• Previous Reviews and Overviews
• Analyses of Specific Drugs and Drug Groups
  • Illicit Drugs
  • Select Adulterants and Diluents
  • Occluded Solvents
• Simultaneous Analyses of Drugs in the Presence of Select Adulterants and Diluents
• Instrumentation Focus
• Analytical Artifacts
• Qualitative Tests
• Sampling Plans
• Source Determination/Impurity Profiling
• Source Determination/Stable Isotope Analyses
• Comparative Analyses
• Reference Standards
• Clandestine Laboratories
• Clandestine Laboratory Appraisals and Safety
• Portable Instrumentation/Trace Detection
• Surveys
• Miscellaneous Topics

Abbreviations

The authors have utilized common abbreviations throughout the review; however, all terms are defined in order to avoid ambiguity with some of the more crowded or obscure acronyms, as follows:

Previous Reviews and Overviews

The forensic analysis of illicit drugs has been the subject of a number of minor review articles and monographs over the past 10 years (1,2,3,4,5,6,7,8,9). In addition, several articles have given more general overviews of the field (10,11). Systematic approaches to substance identification have also been presented (12,13,14), and a number of scientific working groups are currently establishing national/international standards for forensic analysis of illicit drugs (15,16,17(see also:18)). Finally, forensic chemistry has been the subject of several textbooks and chapters in textbooks (19,20,21,22,23,24,25,26).

Analyses of Specific Drugs and Drug Groups

An immense amount of analytical data has been published over the past 10 years for drugs of abuse. "Comprehensive" data compilations (defined in this context as three or more analytical profiles in a specific study) have been previously provided for virtually all "traditional" drugs of abuse, but a number of updated compilations have been provided which reflect improvements in existing instrumentation and/or the advent of new instrumental techniques. In addition, "comprehensive" data compilations have been provided for a number of new drugs of abuse; these include previously unknown "designer," "analog," or "homolog" drugs, and also various pharmaceuticals or industrial chemicals which either had not been previously subject to abuse, or had been only rarely encountered in illicit settings. Furthermore, hundreds of studies which analyzed either specific drugs of abuse or groups of structurally related drugs of abuse, but only by one or two select analytical techniques, have also been provided. [Note that multiple citations are organized as follows: reviews, then overviews, then comprehensive studies, then by specific analytical techniques (alphabetized), and finally in reverse date order (most recent citation first).]

Controlled Substances: Over the past 10 years, the following substances were the subjects of moderate to comprehensive analytical profiling: alkyl nitrites (inhalants) (comprehensive) (27), by GC-IR (28), and by headspace GC/MS (29); Amanita Muscaria by ion-interaction HPLC (30); amphetamine by CE (31), by CE and LC (32), by GC-MS (role of self-protonation) (33), by HPLC (after acetylation) (34), by HPLC using chiral crown ether coated reversed-phase packing (35), and by HPLC using a two-dimensional column-switching chromatographic system with on-line derivatization (36); amphetamine and methamphetamine - (general review of the syntheses and analyses of phenylacetone, amphetamine, and methamphetamine) (37), in abuser's clothing by HPLC with UV and fluorescence detection (38), by CE with cyclodextrins to determine isomers (39), by GC and GC-MS versus internal standards (40), by GC-CI/MS (following derivatization with perfluorinated acid chlorides) (41), by headspace sampling and GC-MS (analysis of betel) (42), by HPLC (43,44), by HPLC for quantitation of clandestinely produced mixtures (45,46), by MS (47), by micro-Raman scattering (48), by surface enhanced Raman scattering detection after modification with 2-mercaptonicotinic acid (49), and by UV/Vis spectrophotometry after derivatization with 1,2-naphthoquinone-4-sulfonic acid (50); amphetamines (review of biological/forensic issues (includes amphetamine and methamphetamine analogues)) (51), by CE (52,53), by CE (chiral) (54), by CE with added anionic chiral selectors (55), by CE and LC (56), by color tests, TLC, GC/MS, GC/IR, plus GC/IR/MS of N-acetyl derivatives (differentiation of side chain isomers of ring-substituted amphetamines (4-Me, 4-OMe, 3,4-MD- amphetamine and methamphetamine)) (57), by CZE (58), by CZE with added cyclodextrins (59), by EI-MS (N-substituted amphetamines) (60), by GC (61), by GC, HPLC, and MS (62), by GC-FTIR (63), by GC/MS (64,65), by GC-MS (differentiation of acylated derivatives of methamphetamine and regioisomeric phenethylamines) (66,67), by HPLC with added cyclodextrins and using a chiral stationary phase (68), by HPLC with fluorimetric detection (69), by HPLC after derivatization with chloroformates (70), by LC with fluorimetric detection after precolumn derivatization with (+)-1-(9-fluorenyl)ethylchloroformate (71), by MECC (72), by negative-ion CI-MS (73), by carbon dioxide negative-ion CI-MS (74), by SFC (75), by SFC, HPLC, GC, and CZE (76), by TLC with diazonium salts as visualization reagents (77), and by GC/FID using nalkanes and other indirect reference standards when no internal standard is available (78); ayahuasca by GC and GC/MSD (79); barbiturates by HPLC with PDA-UV detection (80), by HPLC using 3-(18-naphthalimido)-propyl-modified silyl silica gel as a stationary phase (81), by micro-HPLC with post-column photochemical derivatization (82), by ion-trap and quadrupole MS (83), by IR and MS (84), by mercurimetric potentiometric determination using a solid-state iodide ion-selective electrode (85), by micellar LC (86,87), by SPME and CE (88), by SPME and ion-trap GC-MS (89), by a thermally tuned tandem column (separation of barbiturates and phenylthiohydantoin amino acids) (90), and by two-dimensional overpressured layer chromatography (91); benzodiazepines by CE (92), by electrospray probe/MS (93), by free zone electrophoresis (94), by FT-Raman and FT-IR (95), by HPLC (nitrazepam, diazepam, and medazepam) (96), by HPLC (clorazepate, diazepam, and diltiazem in pharmaceuticals) (97), by HPLC-DAD (98,99), by HPLC using diode-array, electrochemical, and thermospray MS detection (100), by HPLC/electrospray MS-MS (101), by HPTLC (diazepam, chlordiazepoxide, and midazolam) (102), by MECC (103,104), by SERS after adsorption on the Ag colloidal surface (diazepam and nitrazepam) (105), by LC (alprazolam) (106), by microcolumn LC using a cholesteryl-10-undecenoate bonded phase (107), by RP-LC (flurazepam) (108), and by automated SPME-LC/EI-MS (109); 1-benzyl-1-n-butylbarbituric acid (comprehensive) (110); bromazepam by flow injection stopped-flow kinetic determination (111); 4-bromo-2,5-dimethoxyphenethylamine (2C-B or NEXUS) and related compounds (overview) (112), (comprehensive) (113,114), by GC/MS and HPLC (115), by GC-MS and NMR (including analysis of derivatized samples) (116), and by LC and GC/MS (117,118,119); bufotenine (comprehensive) (120,121), and by GC/MS after BSTFA derivatization (122); bufotenine, psilocybin and related indole alkaloids by CE (123), by GC/CIMS (124), by GC/IRD (125,126), by GC/MS (includes general overview) (127), and by MS (128); ["Love Stone" (contains bufotenine) (overview) (129), (overview and GC/MS) (130), and by GC/MS (comparison with Chinese "Chan Su") (131)]; cathinone (alpha-aminopropiophenone) (review with 79 refs) (132), (comprehensive) (133), by NMR (enantiomeric determination of N-acetylcathinone) (134), and by spectrophotometric detection (135); 2-chloro-4,5-methylenedioxymethamphetamine (comprehensive) (136); clenbuterol by CE (chiral analysis with added CD's) (137), by EKC (epinephrine, terbutaline, clenbuterol, and salbutamol) (138), by flow-injection fluorimetry (139), by GC after derivatization and electrospray MS (140), and by RP-HPLC (141); cocaine by CE (simultaneous analysis of coca alkaloids and sugars in illicit cocaine) (142), by free-zone CE (143), by DSC (and GC/FID) (144), by FT-IR and HPTLC (145), by flow injection analysis with amperometric detection (146), by FTIR, GC/MS, and quantitative GC (cocaine HCl in wax) (147), by GC (cocaine base) (148), by GC/MS after field testing (149), by HPLC (150,151), by HPLC and GLC (152), by an ISFET device, GC, and UV (153), by LC/AP-CI-MS (154), by MS (evaluation of fragmentation patterns (155), by collision induced dissociation MS (156), by MECC (157), by Raman microspectroscopy (158,159), by SPME/GC/MS (methylbenzoate from cocaine) (160), by TLC, GC, UV, and GC/MS (identification of cocaine in samples in the presence of other local anesthetics) (161), and by transmission and internal reflection IR (cocaine base versus HCl) (162,163); cocaine analogs by NMR (164), cocaine base (comprehensive) (165); cocaine-Noxide by LC and MS (166); coca tea by solid-phase extraction followed by GC-MS (167); codeine by chemiluminescence (168), by LC and LC-MS/MS (169), and by NMR (170); codeine pharmaceuticals by CE (171), by free solution CE (172), and by HPLC (173); creatine (comprehensive) (174,175), and by TLC/densitometry (176); cyclofenil (comprehensive) (177); cyclohexyl nitrite (comprehensive) (178); dexfenfluramine by HPLC on a chiral column (179); diazepam by ion-trap and quadrupole mass spectroscopy (180), and by polarography (181); dihydroetorphine and etorphine (comprehensive) (182); 2,5-dimethoxy-4-ethylthiophenethylamine (2CT-2) by IR, GC/IRD, and GC/MS (183); 2,5-dimethoxy-4-(N)-propylthiophenethylamine (2C-T-7) (comprehensive) (184); dimethpramide (comprehensive) (185,186,187); dimethylaminorex (comprehensive) (188); dimethylamphetamine by GC, IR, and UV/VIS (stability study) (189), by GC/MS, HS-GC/MS, and LC-ESI/MS (analysis of dimethylamphetamine pyrolysis products) (190); dragon's blood incense (overview) (191), and by GC/MS (192); ergot alkaloids (review) (193), determination and isolation by LC (194), by LC with fluorescence detection (195), and determination of ergonovine maleate by flow injection analysis with chemiluminescence detection (196); etonitazene (comprehensive) (197); fenethylline by IR, UV, and TLC (198), and by TLC, UV/VIS, and toolmarks (199); fentanyl (review) (200), and by cyclic voltametry (201); fentanyl and fentanyl analogs (review) (202), by RP-HPLC (203), and by GC, GC/MS, and IR (204); Flos Daturae by CE (205); flunitrazepam (Rohypnol) (overview) (206), (comprehensive) (207,208), by color testing (screening) (209), by derivatization followed by TLC with fluorescence detection (urine screening focus) (210), by FTIR, FT-Raman, and NMR (degradation study) (211), and by screening techniques (overview) (212); 4-fluorophenylacetone, 4-fluoroamphetamine and 4-fluoromethamphetamine (comprehensive) (213); para-fluorofentanyl (comprehensive) (214), heroin by bioluminescent assay (215), by CZE (216), by rapid GC (217), by GC/MS, FTIR, and TLC (for determination of heroin base in heroin citrate) (218), by HPLC (degradation study) (219), by IR and TLC (220), by continuous flow IRMS (221), by MECC (222,223), by NMR (224), and by TLC (225); heroin and related morphine alkaloids by HPCE (226); heroin and amphetamine by CE (227); human chorionic gonadotropin (beta subunit) by MS (228); gamma-hydroxybutyric acid (GHB) or gamma-hydroxybutyrate (review) (229), (overview) (230), (comprehensive) (231,232,233), by free zone CE with direct UV detection of GHB (234), by color testing (235), by FTIR and color testing (236), by GC/MS after extraction on a SPME fiber and derivatization with BSTFA (237), by ICP-atomic emission and MS (includes ephedrine) (238), by IR using a 3-bounce diamond ATR element (239), by microcrystal testing with cupric nitrate/silver nitrate solution (240), by NMR (241), and by SPME - GC/quadrupole ion trap spectrometry (242); gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) (interconversion study) (243,244), by CE and HPLC (245), by GC/MS with BSTFA derivatization (246), by HPLC (247), by HPLC/UV-VIS and HPLC/thermospray MS (248), gamma-butyrolactone in wine by GC/MS (249); gamma-hydroxybutyric acid (GHB), gamma-butyrolactone (GBL), 1,4-butanediol (BD), tetrahydrofuran (THF), and/or GHB/GBL analogs (overview, comprehensive) (250), (overview of analysis of GHB, GBL, and BD) (251), (overview of GHB, GABA, and various analogs) (252), by CE (253), (comprehensive) (BD in a liquid exhibit) (254), and by GC/MS and FT-IR (BD) (255); N-(2-hydroxyethyl)-amphetamine (comprehensive) (256,257); N-hydroxy-3,4-methylenedioxyamphetamine by GC-FTIR after derivatization (258); N-hydroxy-3,4-methylenedioxymethamphetamine (comprehensive) (259), and by GC and GC/MS (260); imazalil (comprehensive) (261); imipramine by flow-injection extraction - spectrophotometric determination with methyl orange (262); jimson weed (overview and analysis by GC/MS: 263); ketamine (comprehensive) (264), and by GC and GC/MS (265); khat (Catha Edulis) by GC and GC/MS after derivatization with (R)-(+)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetic acid (266), by GC/MS (267,268,269), by GC/MS/MS (270), by HPLC and TLC (271), and by NMR (272); lorazepam by UV (273); lysergic acid diethylamide (LSD) (review) (274), (overview, comprehensive) (275), (comprehensive) (276), by enzyme immunoassay and immunoaffinity extraction and HPLC-MS (277), by GC (278), by GC/MS using electronic pressure controls and pulsed split injection (279), by GC/MS/FTIR (280), by GLC (281), by HPLC (282), by HPLC and GLC (283), by MECC (284), by NMR (285), and by automated TLC (286); LSD and psilocin - by GC/MS and GC/MS-MS (287); marijuana and related cannabinoids by botanical and microscopic examination and GC/FID (288), by CEC (289,290), by DNA analysis (291,292), by the Duquenois-Levine test (on charred marijuana residue) (293), by fluoroimmunoassay (294), by GC and GC-FTIR (includes ephedrine and pseudoephedrine) (295,296), by GC, HPLC, and TLC (297), by GC/FID (versus cannabidiol as a reference standard (298), (versus cannabinol as a reference standard) (299), by GC/MS (300,301), by HPLC (302,303), by HPLC (seeds) (304), by HPLC of neutral cannabinoids of marijuana and hashish after supercritical fluid extraction (305), by LC/MS and LC/MS-MS (306), by plant propagation (determination of viability of stem cuttings) (307), by SFC/AP-CI-MS (308), by TLC and botanical characterization of morphological features (309), by monoclonal antibody (against tetrahydrocannabinolic acid) (310), and by GC/MS (butyl cannabinoids in marijuana) (311); mescaline in hallucinogenic Cactaccae by ion-interaction HPLC (312), and in peyote by GC/MS (comparison of 6 different extraction procedures) (313); methamphetamine (and related compounds) comprehensive (314), by CE (chiral analysis) (315), by diasteriomeric salt formation (316), by FT-Raman (317), by GC, HPLC, and/or CE following derivatization (for enantiomer determination) (318), by full scan GC-ion trap EI- and CI-MS (319), by GC/MS (improving ion mass ratio performance at low concentrations through internal standard selection) (320), by HPLC with circular dichroism detection for determination of enantiomers (321), by IR (chiral analysis) (322,323), by NMR (chiral analysis) (324), by TD-IMS and SIMPLISMA (325), and by CE with UV and LIF detection (326); methaqualone (review) (327), and by color testing (includes mecloqualone) (328); methcathinone (ephedrone) (review) (329), (comprehensive) (330), by GC and GC/MS (methcathinone and some designer analogues) (331), by GC and GC/MS after chiral derivatization with S-(-)-(trifluoroacetyl)-prolyl chloride (332), by GC/MS (333), and by animal testing (potency comparison of enantiomers; includes syntheses) (334); methcathinone and cathinone (comprehensive) (335); 4-methoxyamphetamine (PMA) and 4-methoxymethamphetamine (PMMA) (comprehensive) (336), and 2-, 3-, 4-PMA, PMMA, and P2P (comprehensive) (337); 3-methoxy-4,5-methylenedioxyamphetamine (comprehensive) (338,339); 2,3-methylenedioxyamphetamines (comprehensive) (340); 2,3- and 3,4-methylenedioxyamphetamines (combined studies) by GC/MS-MS (341,342), by LC and MS (343,344); 3,4-methylenedioxyamphetamines (MDA's) (general review of the syntheses and analyses of MDA's and precursors and related compounds) (345), (comprehensive) (346), by C-13 solid-state NMR (347), by CE (348,349), by field testing (350), bt FT-IR (for tablets) (351), by FT-IR microscope (352), by FTIR and GC/MS (353), by GC (tablets) (354), by GC and GC/MS (355), by GC/MS (356), by HPLC with fluorimetric detection (357), by HPLC with fluorometric detection, using added cyclodextrins (chiral analysis) (358), by HPTLC using 0-benzenesulfonamido-p-benzoquinone for detection (359), by LC (360), by ion trap MS (361), by LC-MS with thermospray, electrospray, and APCI interfaces (362), by RP-LC, GC, and EI-MS methods (363), by NIR and HPLC (of tablets, including MDEA and amphetamines) (364,365), by NMR (366,367), by Raman (368,369), and by SERS (370); methylenedioxycathinones (comprehensive) (371), and by melting points (372); methylenedioxyethylamphetamine (MDEA) (comprehensive) (373,374,375); methylenedioxymethamphetamine (MDMA) (comprehensive) ("crystal" MDMA) (376), by CE (377), by FTIR (for determination of hydration polymorphism) (378 and 379), by C-13 NMR (380), by FTIR (MDMA phosphate) (381), by HPLC (382), and by X-ray crystallography (383); (3,4-methylenedioxyphenyl)-2-butanamines (MBDB's) (comprehensive) (384), by GC/MS and LC (385,386,387,388), and a comparative study of N,N-dimethyl-3,4-methylenedioxyamphetamine and N-methyl-1- (3,4-methylenedioxyphenyl)-2-butanamine (389); 3-methylfentanyl (comprehensive) (390); 4-methylfentanyl (comprehensive) (391); methylmethaqualone by NMR (392); methylphenidate by CE (393); 1-(4-methylphenyl) ethylamine (comprehensive) (394); N-methyl-1-phenylethylamine (comprehensive) (395,396); 4-methylthioamphetamine (comprehensive) (397,398), by GC/MS and FTIR (399), and by LC-MS/MS (400); midazolam by UV/Vis (401); morphine by aqueous and nonaqueous CE (for quantitative determination of morphine in pharmaceuticals) (402), by flow-injection analysis with spectrophotometric determination (403), by HPLC with chemiluminescence detection (404), with a fluoride-selective electrode following derivatization with 1-fluoro-2,4-dinitrobenzene (405), and by displacement TLC (406); nandralone-para-hexyloxyphenylpropionate (comprehensive) (407); nootropics/"smart drugs" (overview) (408); opiate alkaloids by CEC (409), by high-resolution electrospray ionization - IMS/MS (evaluation of opiate separation) (410), by HPLC (hydrocodone in Tussionex) (411), and by HPTLC (oxycodone in pharmaceutical solutions) (412); opium (overview of characterization methodologies: 413), by CE (414), by non-aqueous CE (415), by CE-TOF-MS (416), by GC (quantitative determination of opium alkaloids in opium) (417), by GC/MS (narcotine and papaverine in seeds) (418), by HPLC (419), by RP-HPLC on a base-deactivated stationary phase (420), by HPLC of Sep-Pak C-18 cartridge extracts (421), by MECC (422), by pyrolysis-GC (423), by synchronous excitation spectrofluorimetry (424), by TLC-UV densitometric and GC-MSD methods (425), by UV/VIS (for morphine in opium) (426), and by GC/FID, GC/MS, and GC/FTIR (headspace constituents of opium) (427); opium alkaloids by CE with acidic potassium permanganate chemiluminescence detection (428), by CZE (429), by flow-injection analysis using soluble manganese(IV) for chemiluminescence detection (430), by GC/MS after oxime-TMS derivatization (431), by GC/MS (6-acetylmorphine) (432), by HPLC using porous and non-porous stationary phases (433), by HPLC-DAD (stability of morphine containing solutions) (434), by RP-HPLC (codeine and ethyl morphine HCl in pharmaceutical tablets) (435), by LC (for acetylsalicylic acid, caffeine, and codeine phosphate in pharmaceuticals) (436), (for acetylsalicylic acid, caffeine, codeine, paracetamol, pyridoxine, and thiamine in pharmaceuticals) (437), (for paracetamol, caffeine, and codeine phosphate in pharmaceuticals) (438), by RP-LC (papaverine in tablets) (439), by spectrofluororimetric detection (acetylsalicylic acid and codeine in pharmaceuticals) (440), and by spectrophotometric detection (of noscapine with bromocresol green in chloroform) (441); opium, morphine, and heroin (combined study) (comprehensive) (442); oxazepam by automatic kinetic determination (443); pentobarbital by GC/MS (444), and by HPLC (445); phencyclidine (and 1-piperidinocyclohexane-carbonitrile) (review) (446), by IMS (447), and by IR after liquid-liquid extraction from case samples (448); alpha-phenethylamine (comprehensive) (449,450), beta-phenethylamine (overview) (451,452), and by GC/MS, FTIR, and GC/IR (453); phenobarbital by CE (tablets) (454), by LC (for determination of scopalamine, hyoscyamine and phenobarbital in tablets) (455), by multivariate spectrophotometric calibration (for simultaneous determination of phenobarbital and phenytoin in tablets) (456), and by spectrophotometric determination (457); phenylpropylmethylamine (comprehensive) (458); piperazines (comprehensive) (459); psilocybe mushrooms by DNA (460,461), by IMS and GC/MS (462), by GC/MS and HPLC/UV (463), by morphological, microscopic, microchemical, and HPLC with 266 nm UV detection (464), by TLC, GC/MS, and LC/MS (465), and by TLC and GC/MS (psilocin and psilocybin in developmental mushrooms) (466); Salvia Divinorum by GC/MS (467); secobarbital using C-13 labelled secobarbital as an internal standard (468); sibutramine (comprehensive) (469); steroids (overview) (470), (overview, comprehensive) (471), (comprehensive) (472), by EI, CI, and CI/tandem MS (473), by GC (474), by GC/MS (475), by GC/MS after SFC isolation from aqueous matrices (476), by GC-MS and NMR after derivatization with N-methyl-Nalkylsilyltrifluoroacetamide-I-2 (477), by GLC (478), by HPLC with cyclodextrin coated columns (479), by HPLC with UV/Vis-particle beam MS (480), by HPLC-FTIR (481), by HPTLC and HPLC (482), by MS (of tertbutyldimethylsilyl ether derivatives) (483), by MS/MS (484), by quadrupole ion trap tandem MS (485), by 13C - NMR (486), by MECC (487), by MECC, gradient HPLC, and capillary GC (488), by capillary SFC with FID and ECD (489), and by TLC (490); telazol (comprehensive) (491,492); terbinafine (comprehensive) (493), and by UV and nonacqueous voltametry (494); triazolam by TD-GC (495); tricyclic antidepressants - by electrogenerated chemiluminescence (496); and tryptamines by chemiluminescence (497).

Adulterants, Diluents and Precursors (general overviews of essential chemicals and precursors) (498,499), by GC, HPLC, and CE (500), by LC (for determination of non-UV detectable organic impurities) (501), by various analytical techniques (for determination of "secondary" drugs present in cocaine, heroin, marijuana and phencyclidine) (502); acetaminophen by Raman microprobe spectroscopy (503); acetic acid (in acetic anhydride) by NMR (504), dextromethorphan by MEKC (dextromethorphan, pseudoephedrine and guaifenesin) (505); diethylaminoethylaniline (comprehensive) (506), cis- and trans-2,5-dimethoxy-4,beta-dimethyl-beta-nitrostyrenes by FTIR/Raman (507); dimethylsulfone (overview) (508), (removal by sublimation) (509,510), by GC/MS, IR and GC/IR (in amphetamine and methamphetamine samples) (511); dimethyl terephthalate (and dimethyl phthalate) (comprehensive) (512), differentiation of dimethylterephthalate from dimethylisophthalate by GC/FTIR (513), identification of dimethyl terephthalate in cocaine samples (comprehensive) (514); dipyrone in pharmaceuticals with a flow cell containing gold electrodes (515); ephedrine/pseudoephedrine comprehensive (516), by CE, UV, NMR, and MS (for chiral recognition of the enantiomers of ephedrine derivatives) (517), by CE on a chip with amperometric detection (for chiral analysis) (518), by acetonitrile modified CZE (for ephedrine in ephedra callus) (519), by derivative spectrophotometry and ratio spectra derivative spectrophotometry (for simultaneous determination of pseudoephedrine, dexbrompheniramine, and loratadine) (520), by differential-derivative spectroscopy (assay of ephedrine/theophylline containing pharmaceuticals) (521), by an ephedrine based electrode (522), by a doublemembrane ephedrine selective electrode (523), by flow injection - pulse amperometric detection (524), by GC (for determination of pseudoephedrine and diphenhydramine) (525), by GC/MS (for determination of ephedrine alkaloids and tetramethylpyrazine in ephedra sinica Stapf) (526), by HPLC (for determination of ephedrine, pseudoephedrine, norephedrine, and methylephedrine in Chinese folk medications) (527), by HPLC using chiral stationary phases (for separation of the enantiomers of ephedrine, norephedrine, and pseudoephedrine) (528), by HPLC and CE (discrimination of ephedrine and pseudoephedrine) (529), by HPTLC (for simultaneous determination of pseudoephedrine and cetirizine in pharmaceuticals) (530), by LC (for N-methylephedrine, after derivatization with 9-fluorenylmethyl chloroformate) (531), by LC (for determination of pseudoephedrine and carbinoxamine pharmaceuticals) (532), by proton NMR (for determination of ephedrine, pseudoephedrine, and norephedrine in bulk and dosage mixtures) (533), by RP-HPLC-UV (with data analysis to handle quantitation of overlapping peaks) (534), by SPE-LC/UV (for determination of 7 ephedrine alkaloids in herbal products) (535), by TLC and FTIR (for determination of pseudoephedrine in a pseudoephedrine/chlorpheniramine pharmaceutical) (536), and by impregnated TLC (for direct resolution of (+/-)-ephedrine and atropine) (537); ethoxy-1-(2-nitro-1-propenzyl)benzenes by FTIR and Raman (538); guaifenesin by HPLC (539); 3-hydroxy-N-phenyl-2-naphthalene carboxamide (comprehensive) (540); lactitol in cocaine by NMR and IR (541); 4-(N-methylacetamido)- antipyrine (comprehensive) (542); paracetamol by FTIR (543), by ion chromatography (544), by reflectance NIR spectroscopy (545), by NIR transmittance spectroscopy (546), and by simultaneous stopped-flow determination and FTIR (for paracetamol, acetylsalicylic acid and caffeine in pharmaceutical formulations) (547); pheniramines by CZE (for pheniramine, chlorpheniramine, and brompheniramine) (548), and by an imprinted sensor (for chlorpheniramine) (549); phenylpropanolamine by HPLC in pharmaceutical preparations (using 4-dimethylaminobenzaldehyde) (550); procaine by spectrophotometry (using p-dimethylaminobenzaldehyde) (551); quinine by flow-injection chemiluminescence (552), and by HPLC with polarimetric detection (553); safrole by SFC extraction and GC/MS (for determination of safrole and related allylbenzenes in sassafras) (554); sugars by GC after derivatization with trimethylsilylimidazole (for quantitation of sugars in drug samples) (555), theophylline by adsorptive cathodic stripping voltammetry (556), by a flow fluoroimmunosensor (557), by micellar LC and spectrophotometric detection (558), and by UV and HPLC (559); thiamine by cathodic stripping voltametry (560), by cyclic voltametry and HPLC with amperometric detection (561), by flow injection turbidimetric determination using silicotungstic acid (562), and by spectrofluorometry (563); and triprolidine by a kinetic method based on oxidation w/ KMnO4, with spectrophotometric determination (564).

Occluded Solvents in cocaine by GC/MS (565), in cocaine and heroin by headspace - GC/FID and GC/MS (566), and by SHS-GC/MS (567); in methamphetamine by SPME/GC-MS (characterization of volatile components) (568); and in pharmaceuticals (overview, emphasizing headspace - CGC and impurity profiling) (569), by CGC (570), by wide-bore CGC (571), by CGC-ITD (572), and by automated SHS - CGC-MS (573).

Simultaneous Analyses of Drugs and Adulterants/Diluents

A number of studies have been reported which allow simultaneous identification and quantitation of mixtures of controlled substances and adulterants without separating them into individual components. In general, such techniques may be only employed in select geographical areas in which the submitted exhibits are reasonably consistent (that is, routinely the same adulterants and diluents, at or below a threshold percentage). In most cases, they allow much more rapid sample analysis and throughput without unduly compromising the identification of the controlled substance. Such techniques have been utilized for: cocaine by IR (574,575), by Raman (576,577), by spectrometric methods (578), and by sequential second-derivative spectroscopy (579); and pharmaceuticals by NIR and Raman (580), and by spectrophotometry in conjunction with PLS-1 and PLS-2 data processing methods (581); and for determination of interferences by common diluents in street-level drugs by micro-FTIR (582).

Instrumentation Focus

In addition to the above studies which concentrated on specific drugs or drug groups, there have been a large number of studies which focused on specific instrumental techniques, analyzing two or more unrelated drugs or drug types in order to illustrate the utility of the described methodology, including: capillary electrophoresis: (general reviews) 583,584,585,586,587,588,589,590,591, 592,593,594,595,596,597), (general overview and reviews) (598,599), (general overview, comparing various CE techniques) (600), (review for court admissibility) (601), for separation and permanganate chemiluminescence on-line detection of some alkaloids with beta-cyclodextrin as an additive (602), for on-chip separation of amphetamine and related compounds labeled with 4-fluoro-7-nitrobenzofurazane (603), for enantioselective separations of various amphetamines and methylenedioxyamphetamines using cyclodextrins (604,605), for analysis and confirmation of synthetic anorexics in adulterated traditional Chinese medicines (606), for chiral analysis of drugs (607), for chiral identification of drug isomers (608), for chiral analysis of basic drugs using oligosaccharides (609), for chiral separation of basic drug racemates using linear, neutral polysaccharides (610), for chiral resolution of cationic drugs of forensic interest with mixtures of neutral and anionic cyclodextrins (611), for chiral separation of enantiomers of drugs using beta-cyclodextrin (612), for chiral separation of drug stereoisomers with cyclodextrins (613), for chiral separation of basic drugs using ionic and neutral polysaccharides (614), for ultra-fast chiral separation of basic drugs (615), for illicit drug seizures (616), for CE-TOF/MS of drugs of abuse (617,618), for separation of enantiomers of basic drugs (by affinity CE using a partial filling technique and "1-acid glycoprotein as chiral selector) (619), for separation and identification of amphetamines, methadone, venlafaxine, and tropane alkaloids by CE-electrospray MS (620), for separation and identification of designer drugs with CE-ionspray MS (621), for determination of drug-related impurities (622), for analysis of heroin and amphetamine (623), for simultaneous chiral analysis of methamphetamine and related compounds (624), for routine analysis of methamphetamine, amphetamine, MDA, MDMA, MDEA and cocaine with dynamically coated capillaries (625), for analysis of basic pharmaceuticals by CE in coated capillaries with on-line MS detection (626), for quantitation of common illicit drugs (627,628), for chiral separation of selegiline, methamphetamine, and ephedrine using a neutral beta-cyclodextrin epichlorhydrin polymer (629), for tropane alkaloids in a plant extract (630), for CE-DADelectrospray MS of tropane alkaloids, hyoscyamine, scopolamine, and plant extracts (631), CEC: (introductory overview) (632), for simultaneous separation of acidic, basic, and neutral organic compounds, including strong and moderate acids and bases (633), for analysis of drugs of forensic interest (634); CZE: characterization of drugs of forensic interest by CZE/electrospray ionization MS (635), for chiral separation of amphetamine and phenylephrine, using cyclodextrins (636), for chiral separation of basic drugs using cyclodextrins (637), and for chiral separation of some basic drugs (influence of the buffer organic cation) (638); EKC: for chiral separation of drugs by electrokinetic chromatography (639), for separation of enantiomers and geometric isomers using a charged cyclodextrin (640), and for chiral separation of neutral and basic enantiomers using anionic cyclodextrins (641); MECC: (general review) (642), for chiral differentiation of pharmacologically active substances by cyclodextrin-modified MECC using a bile salt (643), for analysis of controlled substances, using different micelles (644), and for analysis of phenethylamines (645); MEKC: for separation of sympathomimetic amines of abuse and related compounds (646); non-aqueous CE: for analysis of drugs (647,648,649,650), for analysis of drugs by nonaqueous CE with electrochemical detection (651), and for analysis of tropane alkaloids and amphetamine derivatives (652); polymethod: characterisation of retention in micellar HPLC, in MEKC and in MEKC with reduced flow (653), complementary use of CZE and MECC for mutual confirmation of results in forensic drug analysis (654), and the study of the CZE behavior of selected drugs and its comparison with other analytical techniques for their formulation assay (655); general: CE using polyacrylamide-coated columns (656,657), effect of methanol in sample solution on an electropherogram (658), evaluation of the use of cyclodextrins in chiral separation of basic drug substances by CE (659), improved chiral separation of basic compounds using beta-cyclodextrin and tetraalkylammonium reagents (660), quantitative aspects of the application of CE to the analysis of pharmaceuticals and drug related impurities (661), separation selectivity in chiral and achiral CE with mixed cyclodextrins (662), and use of large-volume sample stacking for selected drugs of forensic significance (663); fluorescence spectroscopy (review) (664); gas chromatography and gas chromatography/mass spectrometry: (general reviews (books)) (665,666), to distinguish amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine from other sympathomimetic amines following derivatization with propyl chloroformate (GC/CI-MS) (667), to distinguish and quantify the enantiomers of amphetamines, phenol alkylamines, and hydroxyamines following stereospecific derivatization (CGC/MS) (668), for enhanced detection of trace-level controlled substances using GC/MS with pulsed splitless injections (669), for the quantitation of cocaine, heroin, diazepam, methaqualone, codeine, and oxycodone (GC) (670), forensic analysis by GC with dual MS and NPD detection (671), by GC with surface ionization detection (672), using isotopic analogues as internal standards (673,674,675), by MS and electrospray ionization MS (676), with a programmable temperature vaporizing injector and cold on-column injector (677) by rapid GC (678), by secondary electrospray IMS/MS (679), by TLC and GC/MS (680), by wide-bore column GC-NPD (681), a dual internal standard method for screening by GLC at the one percent level (682), internal quality control of a general GC drug screen in forensic toxicology (683), use of MSD's for identification of unknowns (684), normalization of residual ions after removal of the base peak in EI-MS (polydrug study) (685), practical determination of GC-MS limits of detection (686), sample concentrator for sensitivity enhancement in chromatographic analyses (687), SPME-GC (review) (688), and trace analysis by splitless GC/MS (689); high-performance liquid chromatography (and tandem HPLC techniques): general overview (690), (recent progress in HPLC analyses for drugs of abuse) (691), for analyses of barbiturates, LSD, MDA, and psilocybin (HPLC using continuous online post-elution photoirradiation with diode-array UV or thermospray-MS detection) (692), to separate and identify cocaine, morphine, heroin, codeine, papaverine, benzocaine, procaine, and lidocaine (HPLC-DAD) (693), for the rapid analysis of illicit heroin and cocaine samples (HPLC-DAD and CGC/NPD) (694), for assaying morphine and hydromorphone in pharmaceuticals (695), for direct chiral resolution of phenylalkylamines (using a crown ether chiral stationary phase (includes amphetamine and cathinone)) (696), for the simultaneous determination of triprolidine, pseudoephedrine, paracetamol, and dextromethorphan (697), for drug screening (698), for analysis of drugs of forensic interest (RP-HPLC) (699), for analysis of alkaloid drugs of forensic interest (RP-HPLC-PDA) (700), for analysis of some alkaloids on unmodified silica gel with aqueous-organic solvent mixtures (701), for determination of alkaloids in foods (multi-detector HPLC) (702), for detection in the forensic sciences (LC-PDA) (703), to determine the enantiomeric composition of abused drugs (704), for determination of illicit drugs and related substances (HPLC with an electrochemical coulometric-array detector) (705), for forensic analyses (on-line HPLC/FAB-MS) (706), for purity testing for tropane alkaloids (707), for resolution of racemic drugs (using a new chiral column based on silica-immobilized cellobiohydrolase) (708), to study the effects of chromatographic conditions on the retention indices of forensically relevant substances (RPHPLC) (709), and for analysis of pharmaceuticals and drugs (HPLC using unmodified silica and polar solvents) (710); HPLC retention indices: (711,712,713); infrared and Raman spectroscopy: (minor review of IR and Raman for detection of narcotics) (714), (general review of Raman of narcotics and explosives) (715), FTIR and microcrystal tests for rapid identification of drugs (716), FTIR microspectrophotometry of illicit drugs (sample preparation) (717), FT-NIR for validation of controlled substance identifications (718), NIR for identification of drugs and various adulterants/diluents (719), NIR, FT-Raman, and DR-FTIR for non-destructive identification of Chinese traditional drugs (720), GC-FTIR for screening of hallucinogenic and stimulant amphetamines (721), vapor-phase FTIR for identification of novel illicit amphetamines (722), HPTLC-FTIR for identification of LSD, MBDB and atropine (723), use of a diamond anvil cell with a beam condenser and an FTIR microscope for analyses of some particulate drug mixtures (including cocaine, heroin, and methamphetamine) (724), internal reflectance spectra library (725), FT-Raman for nondestructive determination of raw plant medicinal drugs (726), filtered fiber optic Raman probes for analysis of illicit drugs (727), micro-Raman for identification of narcotics (including opium alkaloids) (728), SERRS for drug analysis (729), and evaluation of silver substrates for SERRS of cocaine and other stimulant drugs (730); ion chromatography: for determination of ionic compounds, exicipients, and contaminants in drug evidence (731); microscopy: (general overview) (732), and videomicroscopy (733); nuclear magnetic resonance spectroscopy: (general review) (734), for assessing drug enantiomeric composition (including amphetamine) (735), for chiral identification and determination of ephedrine, pseudoephedrine, methamphetamine, and methcathinone (includes GC analyses) (736), to identify impurities in drug substances (by LC-NMR) (737), and for routine analyses (738,739); phosphorimetry: of barbital, codeine, morphine, and practolol after labelling with dansyl chloride (740); robotics and/or specialized computer programs: (overview and review) (741), for automated CGC heroin analysis (742), combined Rf and UV library search software for TLC and RPTLC (743), a computerized IR search system (744), for optimized analysis of heroin by RP-HPLC (745), to evaluate an HPLC column's performance (746), and to optimize gradient and isocratic HPLC analyses (747); supercritical fluid chromatography: (general reviews) (748,749), and for extraction of tropane alkaloids (including cocaine) from E. coca extracts (750); thin layer chromatography: (general review) (751), TLC/DAD for forensic analyses (752), overpressured TLC (for determination of morphine, codeine, heroin, opium alkaloids, nicotine, amphetamine, cocaine, and LSD) (753), TLC for separation of cocaine, pramocaine, fentanyl, and diphenhydramine (754), and TLC with a special visualization reagent for tertiary amines (including dimethylamphetamine, flunitrazepam, methamphetamine, methaqualone, nicotine, theophylline, triazolam, and others) (755); and miscellaneous: Comparison of IR and MS for drug analyses (756).

Analytical Artifacts

GC and GC/MS are the current methods of choice for routine screening, identification and quantitation of controlled substances. However, the use of high-temperature injectors can produce artifacts via unimolecular rearrangements of and/or intermolecular reactions between the various components (including even the injection solvent). Artifacts are also possible in other techniques. Over the past 10 years, artifacts have been reported for: cannabinoids: nitrites in cannabinoid analyses (urine testing focus) (757,758,759); cocaine: determination of ecgonidine methyl ester vapor pressure (760), identification of methyl esters of ecgonine as injection port produced artifacts from cocaine base (crack) exhibits (761); heroin: identification of a heroin/chloroformimpurity reaction product (762); morphine and codeine: hydromorphone and hydrocodone interference in GC/MS assays for morphine and codeine (763); phenethylamines: artifacts in the GC analysis of amphetamine and MDA (764), GC/MS identification of amine-solvent condensation products formed during analysis of drugs of abuse (from ethanol with amphetamine, MDA, and beta-phenethylamine) (765,766), conversion of ephedrine to methamphetamine and methamphetamine-like compounds during and prior to GC/MS analyses of heptafluorobutyrate and carbethoxyhexafluorobutyrate derivatives (urine testing focus) (767) identification of a GC/MS artifact peak as methamphetamine (768), matrix effects in the IR of methamphetamine salts (769,770), and a procedure for eliminating interferences from ephedrine and related compounds in the GC/MS analysis of amphetamine and methamphetamine (771); piperonal: an artifact in the GC analysis of piperonal (772); and miscellaneous: influence of large amounts of drugs on the peak areas of their coinjected deuterated analogues measured with APCI-LC-MS (773), and a simple software procedure to determine if a GC/MS blank injection is contaminated (774).

Qualitative Tests

Spot tests are a mainstay of forensic analysis of controlled substances, and offer a reliable means for very rapid screening of submitted exhibits. Over the past 10 years, the following qualitative testing studies were reported: (general overview) (775), (textbook) (776), (review of color comparisons in forensic science, including drug color tests) (777), for anhydrous ammonia (778), for cocaine (mechanistic study of the Scott Ruybal test) (779), for drugs of abuse (12 spot tests) (780), for lithium (781), for pemoline, fenozolone, and thozalinone (color tests) (782), and for red phosphorus (783,784,785).

Sampling Plans

Large drug seizures are almost invariably comprised of multiple units of a standard container size (for example, several thousand 1 kilogram packages of cocaine). Comprehensive analysis of such seizures is a daunting and prodigiously labor intensive task; therefore, statistically based sampling plans are utilized that enable valid assessment of an entire shipment based on analyses of a select number of representative, randomly selected exhibits. The classic study in this field (by Frank, Hinkley, and Hoffman) was reported in 1991, but is included here as critical background (786). Over the past 10 years, the following additional studies were reported: (overviews and general discussions) (787,788,789,790,791), and case studies of heroin (792,793,794).

Source Determination/Impurity Profiling

Determination of synthetic route origin (including processing variants) and/or geographical origin is important for developing tactical and strategic intelligence. Historically, source determination has been conducted by in-depth impurity profiling; that is, determining discriminatory marker compounds and/or ratios of marker compounds which are characteristic of origin. More recently, trace element analyses and (especially) stable isotope analyses (vide infra) have increased the confidence of geographical sourcing; this aspect of source determination is rapidly expanding. Finally, increasingly sophisticated pattern recognition techniques (often neural network based) have been employed to handle the enormous databases generated by source determination programs. A large number of source determination studies have been reported over the past 10 years: (general discussions) (795,796), (pattern recognition techniques screening for drugs of abuse (illicit amphetamines) with GC-FTIR) (797); amphetamines: systematic approach to profiling amphetamines (798), automated GC method for amphetamine profiling (799), amphetamine profiling in the UK (800), from arylpropenes with acetonitrile and sulfuric acid (Ritter reaction) (801), of Leuckardt amphetamine (802,803,804,805), from 1-phenyl-2-nitropropene (806,807), improved data processing for amphetamine profiling (808), from phenylacetone synthesized from phenylacetic acid (Leukardt reaction) (809), and a pan-European method for profiling amphetamines (810); amphetamines and marijuana: of impurities (811); cocaine: reviews (812,813,814), comprehensive profiling (815,816,817,818), of 2-carbomethoxy-3-alkyloxy- and heteroaroyloxy substituted tropanes in cocaine (819), of 2-carbomethoxy-3-oxo analogs in cocaine (820,821), of chlorinated cocaines from cocaine treated with bleach (822, see also:823), of cuscohygrine in cocaine (824), of heteroaroyl analogs in cocaine (825), of 1-hydroxytropacocaine in cocaine (826), of hygrine in cocaine (827), of hygrine and cuscohygrine in cocaine (828), of norcocaine in cocaine (829), of occluded solvents in cocaine (effects of microwave radiation on solvent profiles) (830), of pharmaceutical cocaine (831), of pseudococaine in cocaine (832), of trace metals in cocaine (833), of trimethoxy analogs of cocaine, cinnamoylcocaine, and tropacocaine in cocaine (834), of truxillines in cocaine (835), of truxillines and similar high molecular weight impurities in cocaine (836), of illicit cocaine by X-ray Diffractometry (also GC and GC/MSD) (837); cocaine and heroin: (combined studies) of trace metals in cocaine and heroin (838,839,840,841,842,843,844,845,846), and by palynology (pollen analysis) (847); of occluded solvents in cocaine and heroin (848); ephedrine: by microscopic examination (849); fentanyl: prepared from 1-phenethyl-4-piperidone (850); heroin: overview (851), (review) (852), of acid and neutral impurities in heroin (853), of anions and cations in heroin (854,855), of basic byproducts and adulterants in heroin (856), of impurities in heroin (857,858,859,860,861), of metal contamination in heroin (862), of O6-monoacetylmorphine in "homebake" heroin (863), of trace elements in heroin by ICP-MS (864,865), of trace organic impurities (866); marijuana: of cannabidiol and delta-9-THC in stored marijuana (867), of impurities in hashish (868,869), of impurities in marijuana (870,871,872), of natural constituents in marijuana (reviews) (873,874), and of marijuana DNA (875,876,877,878,879,880,881,882,883); methamphetamine: review (UNDCP) (884), overview (885), generic articles on impurity profiling (886,887), of N-acetylmethamphetamine in illicit methamphetamine (888), of chloroephedrine and aziridines in methamphetamine (889), of impurities in methamphetamine (890,891), of inorganic impurities in methamphetamine (892), of methamphetamine synthesized from allylbenzene (893,894,895), of impurities in methamphetamine synthesized via HI/red P (896), of methamphetamine synthesized via HI/red P (focusing on reaction byproducts of common cold tablet ingredients) (897,898), of methamphetamine containing a hydrocarbon wax (899), of methamphetamine synthesized from pseudoephedrine tablets (900), of trace elements in methamphetamine (901), of methamphetamine seized in Australia (overview and development of a national database) (902), of methamphetamine seized in Japan (903,904, and overview: 905), and of methamphetamine seized in Korea (906); 4-methoxyamphetamine: of impurities (907); methylenedioxyamphetamines: overview of approach in Australia (908), of impurities in methylenedioxymethamphetamine (909,910), of precursors, intermediates, and reaction byproducts for methylenedioxymethamphetamine (911), of impurities in methylenedioxymethamphetamine and amphetamine (912), of impurities in methylenedioxyamphetamine and methylenedioxymethamphetamine (913,914), determination of synthetic route markers for methylenedioxyamphetamine and methylenedioxymethamphetamine (915), of methylenedioxymethamphetamine tablets by logo and headspace comparisons (916), of commercially available methylenedioxyphenylacetone (917), from the Ritter reaction (using safrole) (918), of methylenedioxyphenylacetone and methylenedioxyamphetamine synthesized from isosafrole (919,920), and of methylenedioxyamphetamine synthesized from nitoethane and piperonal (921); nicotine: (overview of tobacco smoke) (922); opium: of opium alkaloids (for origin determination) (923), of proteins in opium latex (924); pharmaceuticals: overview (925), of impurities (926,927,928); phenyl-2-propanone: of illicit phenylacetone synthesized from phenylacetic acid with acetic anhydride versus lead (II) acetate (929); precursors: of essential oils used as precursors in the synthesis of phenethylamine-type designer drugs (930), and testosterone undecanoate: of impurities (931).

Source Determination/Stable Isotope Analyses

Historically, processing origin could be reasonably correlated with geographical origin. However, the expansion of drug producing regions and the concommitant convergence of processing techniques, along with the international exchange or sale of precursors (for example, 3,4-methylenedioxyphenylacetone) or crudely refined controlled substances (for example, morphine or heroin base) across the world, have mandated more sophisticated analyses. Because the natural abundances of the stable isotopes of hydrogen, carbon, nitrogen, and oxygen vary across the world, and their incorporation into natural products is unaffected by subsequent illicit processing, stable isotope analyses offer a powerful tool for determining "true" geographic origin (that is, not indirectly inferred based on processing methodology). Recent advances in instrumentation (notably isotopic ratio mass spectrometry and high field nuclear magnetic resonance spectroscopy) have enabled the determination of the isotopic makeup of controlled substances with reasonable precision and accuracy. To date, only cocaine and heroin have been subjected to comprehensive studies; however, this field is expected to expand to other controlled substances over the next decade. Recent reports include: (overviews) (932,933,934); cocaine: by carbon-13 isotope analysis: (935,936), by IRMS and trace alkaloid analysis (937); cocaine and heroin: by IRMS (938), by site specific deuterium-NMR (939); and heroin: by GC/IRMS (940), and by GC/MS and GC/IRMS (941).

Comparative Analyses

Establishing commonality of origin between 2 or more exhibits requires systematic application of detailed impurity profiling. Comparative analysis does not require formal determination of synthetic, processing, or geographical origin, but rather determination of "degree of match" between profiles (usually trace-level chromatographic analyses; however, establishment of synthetic, processing, or geographical origin is a common spinoff of comparative analysis protocols). Studies reported over the past 10 years include: (general overviews) 67 (942,943); amphetamine: computerized comparisons of Leuckart amphetamine (944); cocaine: (overview of methodologies) (945), database for comparison (946), by CGC/ECD (947), by CGC/NPD (948), comparison of crack cocaine by matching fracture lines between pieces (949), cocaine comparison court case (950), by rapid GC (951), by HPLC-DAD (952), by a neural network (953); hashish: by HPLC, GC, and AA (954); heroin: (general overview) (955), by CGC (956), computerized comparison (957), predictive model (958), harmonization study for retrospective comparisons (959,960), of SWA heroin by GC (961); marijuana: comparison by RAPD and HPLC (962); methaqualone: tablets by NIR reflectance spectra (963); methylenedioxymethamphetamine: by natural isotope abundances (964); opium: by RAPD, HPLC, and ELISA (965), pharmaceuticals: evaluation of neural networks (966); and tablets and capsules: indices of physical characteristics (967,968).

Reference Standards

Accurate analyses of controlled substances and related analogs require high purity standards, including isotopically labelled analogs. Structurally related compounds are also needed as internal standards for chromatographic analyses. Reports over the past 10 years include: (general reviews) (969,970); bufotenine (and related tryptamines): (971), butalbital: (972); cannabinoids: (973,974); cocaine: (975,976), aza analogs of cocaine (977), deuterium-labelled cocaine, cocaethylene and metabolites (978), cocaine by one step esterification of benzoylecgonine (979), 6- and 7-hydroxylated cocaines (980), C-3 alkyl analogs of cocaine (981); lysergic acid diethylamide (982,983); d- and l-methamphetamine: via optical resolution (984), "Ice" methamphetamine (985); methcathinone: (986); methohexital: (987); morphine: (988,989); polydrug: (N-ethylmethylenedioxyamphetamine, N-hydroxymethylenedioxyamphetamine, mecloqualone, 4-methylaminorex, phendimetrazine, and phenmetrazine) (990), (O6-monoacetylmorphine, methamphetamine, methylenedioxyamphetamine, methylenedioxymethamphetamine, methylenedioxyethylamphetamine, and N-methyl-3,4-methylenedioxyphenyl-2-butanamine, from seized drugs) (991), and a reference garden of hallucinogenic and narcotic plants in Australia (992); (1S,2S)-pseudoephedrine: (993); and psilocybin and O-acetyl psilocybin (994).

Clandestine Laboratories

The illicit production of drugs is a dynamic and constantly changing field. Reports over the past 10 years included: (general review) (995), amphetamine (996,997,998), failed synthesis of amphetamine (999), amphetamine in methamphetamine (1000), analyses of inorganic components found in clandestine drug laboratory evidence (1001), arsenic oxide (potential reagent in methamphetamine synthesis) (1002), Birch reduction (general review) (1003) (overview of developments in the midwestern US (1004), cocaine (1005,1006), concealment and trafficking (1007), 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2) (1008), ephedra (1009,1010), ephedrine and/or pseudoephedrine (1011,1012), etonitazene (1013), fentanyl (1014), freons in methamphetamine production (1015,1016,1017), hash oil (1018,1019), heroin (acetylated opium) (1020), heroin (review) (1021), hydriodic acid for methamphetamine production (1022,1023,1024), hypophosphorus acid for methamphetamine production (1025), inorganic acids (1026,1027), iodine (GC/MS identification) (1028,1029), lysergic acid amide from morning glory seeds (1030), lysergic acid diethylamide (1031), marijuana (1032,1033), methadone (1034), methamphetamine (1035,1036,1037,1038,1039,1040,1041), methamphetamine (by dissolving metal reduction) (1042,1043,1044), methamphetamine in Taiwan (1045), methaqualone and analogs (1046), methcathinone (1047), methylenedioxymethamphetamine (1048), methylenedioxyphenethylamines (1049), morphine (by dealkylation of codeine) (1050), overview of illicit drug production in the Czech Republic from the 70's through the 90's (1051), phencyclidines (1052,1053,1054), phenylacetone and methylenedioxyphenylacetone (1055,1056), piperonal (1057), polydrug (methamphetamine, phenylacetone, methylenedioxyamphetamine, and methaqualone) (1058), steroids (1059), substitution of white phosphorus for red phosphorus in hydriodic acid reduction laboratories in Idaho (1060), delta-9-THC precursors (1061), delta-9-THC acetate (1062), unusual defense to charge of MDMA manufacture (1063), and an unusual designer drug laboratory (polydrug) (1064).

Clandestine Laboratory Appraisals and Safety

The rapid expansion of clandestine laboratories in the US over the past 15 years has resulted in a large number of studies concerning proper assessment and safe dismantling, including reports on: assessment and remediation of contaminated sites (1065), clandestine laboratory production capabilities (1066), confined space laboratories (1067,1068,1069,1070), decontamination of biohazardous evidence (1071), determination of occupational exposure to cocaine by crime lab personnel (1072), determination of volumes in clandestine laboratory reaction vessels (1073), environmental impact and adverse health effects of the clandestine manufacture of methamphetamine (1074), field methods to render safe pressurized tanks of ammonia at clandestine labs (1075,1076), hydrogen sulfide fatality (1077), OSHA and NIOSH regulations (1078,1079), phosphine gas exposure from a methamphetamine laboratory investigation (1080), phosphine gas fatalities (1081,1082), phosphine gas detection and monitoring instrumentation (1083), safety training for clandestine laboratory investigators (1084,1085), supplier of 22-liter flasks put on notice (1086), training (1087,1088), triacetonetriperoxide causes explosion during analysis (1089), and useful websites for personnel involved in forensic laboratories and/or clandestine laboratories (1090).

Portable Instrumentation/Trace Detection

New world trade agreements and the easing of formerly restrictive national and international borders have resulted in dramatic increases in cargo transshipping and personal travel, thereby complicating drug inspection and interdiction efforts at POE's. The need for rapid and accurate screening, and high sample throughput, requires on-site equipment capable of assessing humans, animals, and a vast array of shipping containers. In addition, on-site equipment is needed for proper assessment of clandestine laboratories. However, the typical size and operational requirements of most laboratory instrumentation preclude their use in field settings. This has resulted in a growing industry dedicated to development of man-portable, field rugged equipment for detection and identification of controlled substances. Many of the pertinent studies are proprietary, but a large number have nonetheless been reported over the past 10 years: general: (reviews) (1091,1092,1093,1094,1095), (general assessments) (1096,1097,1098,1099), appraisal of drug detection scenarios - operational analysis for drug detection (1100), and determination of high-risk cargo (1101); amperometric assay: for opiates (1102); biosensor technologies for the detection of illegal drugs (1103,1104,1105,1106,1107), antibody-based field kits for cocaine and heroin (1108), a fiber-optic cocaine biosensor (1109), an ISFET device for cocaine analysis (1110), the use of heroin esterase in the development of a biosensor (1111), and use of recombinant DNA in the design of a heroin sensor (1112); calibration standards: for narcotics detection devices (1113); correlated column micro-GC: for the detection of contraband drugs in cargo containers (1114); field ion spectrometry: (1115); gamma ray detectors: (1116,1117,1118); gas sensor arrays for drug "aroma" detection (1119); immunoassay based detection systems: (1120,1121) and similar technologies (1122); DRUGWIPE: (1123); ion mobility spectrometers: (1124,1125,1126,1127,1128), detection of cocaine and heroin by a custom built IMS (1129), detection of drugs of abuse in Customs scenarios using IMS (1130), use of fluorescence spotting to identify areas for IMS (1131), detection of methamphetamine and ephedrine in abandoned clandestine laboratories with IMS (1132), differentiation of methamphetamine versus nicotine using IMS (1133), DSP techniques for narcotic detection using IMS (1134), field applications of IMS (1135,1136), and use of SPME with IMS (1137); ion trap mobility spectrometers: (1138,1139,1140); laser-based near- and mid-IR: (1141); neutron-based technologies: (1142,1143,1144,1145,1146,1147,1148,1149,1150,1151), combined neutron and gamma ray detection (1152), evaluation of neutron techniques for illicit substance detection (1153,1154,1155), and pulsed fast neutron analysis (1156,1157); N-14 nuclear quadrupole resonance: (1158,1159,1160,1161); particle detection: cocaine phenomenology study (1162), confidence in the detection of cocaine particulates by IONSCAN and SENTOR systems (1163), particle generators for testing of particle detection equipment (1164), particle size distribution of cocaine HCl (1165), particle size analysis of six illicit heroin preparations seized in the UK (1166), use of methylene blue as a simulant for cocaine HCl and heroin HCl (1167), test material for narcotics detection equipment (1168), and voltametric determination of cocaine microparticles (1169); piezoelectric ringing: (1170); portable GC/MS: for clandestine laboratory investigations (1171,1172); Raman spectroscopy: (1173,1174,1175), minor review of applications (1176), near-IR Raman to identify illegal drugs in solid mixtures (1177), and Raman microscopy for direct 2-D imaging of explosives and drugs (1178); human screening: of internal body packers by magnetic resonance (1179), of internal body packers by X-ray scanning (1180), of packages on persons by X-ray imaging (1181,1182), of prisoners in the Canadian Correctional Service by IMS and ion trap mobility spectroscopy (1183), and a survey of current portal technology for screening people for illicit substances (1184); SENTOR: recent developments (1185); solid-state gas sensors: (1186); surface ionization detection: (1187); surface acoustic wave (SAW) detectors: detection of taggants and volatiles by SAW/GC (1188), and portable detection system for illicit materials based on SAW resonators (1189); surface sampling: detection of drugs on vehicle surfaces (general study) (1190), and study of surface sampling procedures for improved sampling/detection protocols (1191); tandem mass spectrometry (CONDOR): (1192,1193); testbeds: chemical vapor test-beds (1194), and a nonintrusive inspection technology testbed (1195); TOF-MALDI mass spectrometry: (1196); vapor detection: analysis of volatiles from cocaine (1197,1198,1199), analysis of vapors from cocaine and heroin with the aid of SPME (1200), cocaine and heroin vapor pressures (1201), detection of cocaine in cargo containers by high volume vapor sampling (field test) (1202), and formation of methyl benzoate from cocaine HCl under different temperatures and relative humidities (1203); and X-ray technologies (1204,1205).

Surveys

Critical to total threat assessments and the monitoring the effectiveness of counter-narcotics efforts are surveys of drug use and related topics. Over the past 10 years, surveys have been reported for: amphetamine: of global amphetamine abuse (1206,1207), and of amphetamine type drugs used in Bulgaria (1208); cocaine: of adulterants in cocaine in Rome in 1996 and 1997 by GC and GC/MS (1209), of cocaine seized in Spain 1985-1993 (1210), of intralaboratory precision of cocaine analysis by CGC (1211), and of occluded solvents in cocaine 1986 - 1991 (1212); designer drugs: (review) (1213), of amphetamine-type designer drugs in Europe (1990-1996) (1214), of designer drugs in Canada (1215), of designer drugs in the European Union (1216,1217), and of designer drugs in Italy (1218); drug use (general): global trends - 2000 (1219), global trends - 1999 (1220), of drug abuse in Hungary (1221), of Irish drug seizures (1222), of drug usage in San Diego County 1990-1997 (1223), of drug contents of powders and other illicit preparations in the UK (1224), of drugs imported into the UK (1225), and of drug abuse in Western Denmark during the eighties (1226); flunitrazepam: of Rohypnol Tablets (1227); heroin: of heroin in Australia (in Sydney in 1997) (1228), of heroin in Denmark, 1981-1992 (1229), of heroin seized in France (1230), of heroin in Israel during 1992 (1231), of noscapine in heroin in Slovenia, 1997 - 1999 (1232), of heroin seized in Spain (1233), of heroin in Andaluza, Spain (1234), of heroin in the UK, 1984 to 1989 (1235), of retail level heroin purchases in the US during 1992 (1236), of the cutting of heroin in the US in the 1990's (1237), and of cutting of heroin in New York City (1238); LSD: of LSD blotter papers logos (1239); marijuana: of the THC content of cannabis cultivated in Austria (1240), of recent developments in Europe concerning licit cultivation of cannabis (1241), of the cannabinoid content of marijuana seized in Greece (1242), of delta-(9)-THC content in cannabis of Greek origin (1243), the potency of cannabis in New Zealand, 1976 to 1996 (1244), of cannibis resin and cannibis seized in the Republic of Ireland (1245), of trends in illicit cannabis cultivation in the UK and Northern Ireland (1246), of potency trends of 9-THC and other cannabinoids in confiscated marijuana from 1980-1997 in the US (1247), of the global situation of cannabis consumption, trafficking, and production (1248), and of recent developments in cultivation and quality of illicit cannabis (worldwide) (1249); methylenedioxyamphetamines: of MDMA, MDA, MDEA, NEXUS, and MBDB tablets seen in southwestern Spain (1250,1251), and of MDMA, MDEA, and MBDB tablets seen in the United States (1252,1253,1254,1255); polydrug: of heroin, cocaine, and cannabis from British Columbia (1256), and of heroin and cocaine seized in a Swiss town (1257); UNDCP Reports (by year): World Drug Report - 2000 (1258), List of Narcotic Drugs under International Control (INCB "Yellow List") - 1999 (1259), (INCB "Green List") - 1999 (1260), (INCB "Red List") - 1999 (1261), Report of the International Narcotics Control Board - 1999 (1262), Manufacture of Narcotic Drugs, Psychotropic Substances, and their Precursors - 1999 (1263), Narcotic Drugs Estimated World Requirements - 1999 (1264), Precursors and Chemicals Frequently Used in the Illicit Manufacture of Narcotic Drugs and Psychotropic Substances - 1999 (1265), Psychotropic Substances - Statistics - 1999 (1266), Terminology and Information on Drugs - 1999 (1267), the World Drug Report - 1997 (1268), and Supply of and Trafficking in Narcotic Drugs and Psychotropic Substances - 1996 (1269); miscellaneous: of adolescents' use of embalming fluid with marijuana and tobacco (1270), and of crime laboratory proficiency testing results 1978-1991 (1271).

Miscellaneous Topics

The following topics of peripheral interest to the analysis and detection of drugs of forensic interest were also reported from 1992 - 2001: angel trumpet: overview (1272); amphetamine: a review of U.S. statutes on methamphetamine and how they led to an increase in illicit amphetamine production (1273); ayahuasca: notes on an Ayahuasca court case in Holland (1274,1275); barbiturates: charge transfer complexes with phenytoin (1276); canines: use of activated charcoal to circumvent canine detection of concealed narcotics (1277), analysis of volatile drug components and their relevance to canine alerts (1278), characterization of the Auburn Olfactometer (1279), of cocaine on currency (1280), drug money and detection by canines (1281,1282), scientific protocol to evaluate and certify odor detection by canines (1283), and sensitivity of canines to cocaine HCl and methylbenzoate (1284); (traditional) Chinese medications: overview (1285), manufacturing flaws and misuse of Chinese herbal medicines (1286), determination of some active components in Chinese medicial preparations by CE (1287), screening of Chinese proprietary medications for undeclared therapeutic substances by HPLC and GC/MS (1288), identification of Western medicines as adulterants in Chinese herbal medicines by HPLC and GC/MS (includes diazepam) (1289), screening for chemical drugs used to adulterate in rheumatic and analgesic traditional Chinese medicine by HPLC-DAD (includes diazepam and phenylbutazone) (1290), determination of adulterated chemical drugs in rheumatic and analgesic traditional Chinese medicine by MEKC (includes diazepam and phenylbutazone) (1291), determination of clobenzorex HCl and diazepam adulterated in anorexiant traditional Chinese medicines by MECC (1292), and determination of fluoxymesterone, methyltestosterone and testosterone in adulterated Chinese herbal preparations by HPLC (1293); cocaine: alkaloid content in Erythroxylum Coca tissue during reproductive development (1294), the base-catalyzed C-2 exchange and epimerization of 3-beta substituted 8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylates (1295), biomass accumulation and alkaloid content in leaves of Erythroxylum Coca and Erythroxylum Novogranatense Var Novogranatense grown in soil with varying pH (1296), effects of cyanoacrylate processing (for fingerprinting) on cocaine HCl trace analysis (1297), gas phase detection of cocaine by means of immunoanalysis (1298), protest against cocaine base sentencing (1299), SFC extraction of cocaine from coca leaf (1300), solubility of cocaine in gasoline (1301), and stability of cocaine in Agua Rica/Agua Madre (1302); (analysis for) controlled substances on currency: comprehensive review (covers cocaine, heroin, THC, and phethylamines) (1303), cocaine on currency (1304,1305), cocaine on currency by GC-MS (1306), cocaine on currency by IONSCAN IMS and LC/MS with electrospray ionization or by GC-ITD/MS (1307), analysis of drugs on currency by GC/MS (1308), by MS/MS, TD-MS, and APCI-MS (1309), by tandem MS (CONDOR) (1310,1311), and screening of currency by TD/APCI-MS (1312); designer drugs (unusual): dihydrobenzofuran analogues of hallucinogens (1313), lactam analogs of fentanyl (1314), methylenedioxyisoquinolines (1315), synthesis and pharmacological evaluation of ring-methylated 3,4-methylenedioxyamphetamines (1316), reference directory of designer drugs (1317), 1,2,3,4-tetrahydroisoquinoline analogs of phenylalkylamine stimulants and hallucinogens (1318,1319), and the texts by Ann and Alexander Shulgin (1320,1321); dextromethorphan: (overview) (1322); dimethylamphetamine: mechanistic study of preparation from methylephedrine (1323); ephedrine: extraction of ephedrine from ephedra by SFC (1324); heroin: homogenization of illicit heroin samples prior to analysis (1325); inhalants: general discussions of inhalants and solvent abuse (1326,1327,1328); Internet: discussion of internet resources for forensic science (1329,1330); lysergic acid diethylamide: detection of LSD on blotter papers after processing for fingerprints (1331), and stability of LSD under various storage conditions (1332); marijuana: botanical considerations for forensic investigation of marijuana (1333), embalming fluid-soaked marijuana (compare to Elwood/Fry article) (1334), filtering effects of various household fabrics on the pollen content of hash oil (1335), identification and quantitation of 11-nor-delta(9)-tetrahydrocannabivarin-9-carboxylic acid (1336), manufacture of Cannabis Sativa for legitimate applications (1337), mineral nutrition of Cannabis Sativa L. (1338), and comments on the naming of the Duquenois and related tests for cannabis (1339); mass spectrometry: archive of mass spectral data files on CD-ROM and a computerized database (1340), ion ratio instability of a GC/MS system (1341), and poor reproducibility of in-source collisional AP MS of drugs (1342); methadone: claim that DEA chemists erred in calculating quantity of methadone that could be synthesized from precursor chemicals (1343; and response: 1344); nightshade alkaloids: historical review (1345); opium: historical review (1346), biodiversity of Papaver Somniferum L. (1347), and determination of loss on drying of opium samples using microwave ovens (1348); oxycodone: overview (1349); phencyclidine: ionic associates of phencyclidine with sulfophthaleins and azo dyes (1350); polydrug: hypnotics and sedatives not belonging to the classes of barbiturates and benzodiazepines (1351); poppy tea: case study/overview (1352); thebaine: synthesis from codeine methyl ether (1353); other topics: analysis of clandestine drug records (1354), analysis of drugs in unconventional samples (1355), analysis of false positives in drug proficiency testing (1356), analysis of a fruit juice extract that was suspected to be a narcotic beverage by GC/MS (1357), analysis of plastic packaging to trace the source of illicit drugs (1358), computerized management of a forensic analytical laboratory (1359,1360), considerations for planning and site preparation for modern laboratory instrumentation (1361,1362), development of a forensic evidence protection kit (1363), drug smuggling techniques and problems associated with analysis (1364), drug smuggling by internal body carries (1365), environmental impact of illicit narcotics cultivation and processing (1366,1367), expert evidence and forensic misconceptions of the nature of exact science (1368), GC/MS guide to ignitable liquids (1369), modification of an extraction procedure for acidic and neutral drugs (1370), neural networks in forensic science (overview/general discussion) (1371), protecting group chemistry (1372), separation and identification of drugs of abuse in drug cottons by HPLC coupled with electrochemical array detectors (1373), solid phase extraction for systematic toxicological analysis (1374), the UNDCP Dictionary of Narcotics (1375, and addendum: 1376); and an overview of the United Nations International Narcotics Control Board (1377).

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