井上 博之

PurposeImpurity profiling of seized illicit methamphetamine (MA) provides information on MA manufacturing methods in clandestine laboratories, and this drug intelligence supports formulation of strategies to control MA abuse. In the present study, we developed a simultaneous chiral analysis method for MA and its precursors using supercritical fluid chromatography-tandem mass spectrometry equipped with an enantioselective stationary phase.MethodsChromatographic conditions were optimized by systematic investigation of the flow rate, temperature, back pressure, co-solvent, additive, and mobile phase composition. The ability of the developed method was evaluated using standard and authentic illicit MA.ResultsThe use of a chiral selector in the stationary phase allowed for simultaneous chiral differentiation of MA and its precursors including ephedrine, norephedrine, chloropseudoephedrine, methylephedrine, dimethylamphetamine, and amphetamine. Sufficient limit of detection, repeatability of retention time, and linearity were achieved. A switching valve interfacing a chromatograph and a mass spectrometer enabled analyzing large amounts of MA directly. The application to the authentic illicit MA samples was achieved and revealed the existence of impurities, which was not detected by conventional gas chromatography-mass spectrometry.ConclusionsThe developed supercritical fluid chromatography-tandem mass spectrometry method could be a powerful analytical tool for MA impurity profiling.

The cis and trans isomers of 3-methylfentanyl and its three analogs were chemically synthesized, and these compounds were characterized and differentiated by gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS), and nuclear magnetic resonance (NMR) spectroscopy. The cis and trans isomers of the 3-methylfentanyl analogs were completely separated by GC/MS. Although the high temperature of the GC injection port caused thermal degradation of -hydroxy-3-methylfentanyl, the degradation was completely suppressed by trimethylsilyl derivatization. The isomers were also well separated by LC/MS on an octadecylsilyl column with 10mM ammonium acetate and methanol as the mobile phase. The proton NMR signals were split when the hydrochloride salts of the 3-methylfentanyl analogs were dissolved in deuterated chloroform because stereoisomers were formed by the coordination of the hydrochloride proton to the nitrogen of the piperidine ring of the 3-methylfentanyl analogs.

The enantiomers of methamphetamine were differentiated by supercritical fluid chromatography (SFC) with an enantioselective cellulose-based packed column. The optimization of the chromatographic conditions was achieved by changing column temperature, co-solvent proportion, additive concentration, flow rate and back pressure. In particular, the additive concentration crucially changed the resolution between the enantiomers. After determining the optimized conditions, the enantiomers of methamphetamine were successfully separated. The analytical precision, accuracy and limit of detection were checked by using the authentic standard and seized real samples. We believe that chiral SFC is a promising method for enantioseparation of forensic samples. (C) 2017 Elsevier B.V. All rights reserved.

Hair and nails are often used to prove long-term intake of drugs in forensic drug testing. The aim of this study was to evaluate the effectiveness of drug testing using hair and nails and the feasibility of determining when drugs were ingested by measuring the time-courses of drug concentrations in hair and toenails after single administrations of various drugs. Healthy subjects ingested four pharmaceutical products containing eight active ingredients in single doses. Hair and toenails were collected at predetermined intervals, and drug concentrations in hair and nails were measured for 12months. The administered drugs and their main metabolites were extracted using micropulverized extraction with a stainless steel bullet and were analyzed using liquid chromatography/tandem mass spectrometry. Acidic compounds such as ibuprofen and its metabolites were not detected in both specimens. Acetaminophen, a weakly acidic compound, was detected in nails more frequently than in hair. The maximum concentration of allyl isopropyl acetylurea, a neutral compound, in nails was significantly higher than in hair. Nails are an effective specimen to detect neutral and weakly acidic compounds. For fexofenadine, a zwitterionic compound, and for most basic compounds, the maximum concentrations in hair segments tended to be higher than those in nails. The hair segments showing the maximum concentrations varied between drugs, samples, and subjects. Drug concentrations in hair segments greatly depended on the selection of the hair. Careful interpretation of analytical results is required to predict the time of drug intake. Copyright (c) 2016 John Wiley & Sons, Ltd.

In the study reported here, two glucuronic acid-conjugated metabolites of 4-bromo-2,5-dimethoxyphenethylamine (2C-B)a ring-substituted psychoactive phenethylaminewere chemically synthesized for the first time and a method for analyzing them in urine was developed. -D-Glucuronide of 4-bromo-2,5-dimethoxyphenylethylalcohol was successfully synthesized using methyl 2,3,4-tri--acetyl-1-O-(trichloroacetimidoyl)--D-glucuronate as a glucuronyl donor and boron trifluoride diethylether complex as a Lewis acid catalyst. -D-Glucuronide of 4-bromo-2,5-dimethoxyphenylacetic acid was synthesized by condensing 4-bromo-2,5-dimethoxyphenylacetic acid and benzyl D-glucuronate followed by benzyl group deprotection based on catalytic hydrogenation. Two glucuronic acid-conjugated metabolites of 2C-B in urine were qualitatively and semiquantitatively evaluated via direct liquid chromatography/mass spectrometry (LC/MS) analysis of a diluted urine sample. The simple method proposed is expected to be useful for studying the metabolic fate of 2C-B.

Chromatographic differentiation of the ring-substituted regioisomers of amphetamine (AMP) and methamphetamine (MA) was performed by supercritical fluid chromatography (SFC). The behaviour of the retention against the changes of column temperature and co-solvent proportion was studied. The obtained information facilitated the optimization of the each regioisomer. As a result, 2-, 3-, and 4-ring-substituted analogues of AMP and MA with methyl, methoxy, fluoro, chloro, and bromo groups were separated, generally within 6min. In addition, we found that the separation pattern of the examined regioisomers was classified into two, which depended on the electron donating/withdrawing effect of the substituent. Our results indicate that SFC could be used in forensic drug analysis for fast, reliable identification of structurally similar drugs of abuse. Copyright (C) 2016 John Wiley & Sons, Ltd.

The Scott test, widely used as the field test for cocaine, is performed in three steps. If a sample contains cocaine, blue precipitates appear in step 1, the precipitates are dissolved and the solution turns pink in step 2, and the lower layer turns blue in step 3. However, some pyrrolidine-type cathinones produce cocaine-like results when tested, necessitating modification of the test procedure. Filtration of the second-step mixture weakened the blue color in step 3; however, the blue color did not completely disappear. Adding the Chen-Kao reagent to the test procedure enhanced the differentiation: when the reagent was added to cocaine, the solution was initially turbid, but then became clear over time; its addition to cathinones resulted in turquoise or light sky-blue precipitation. These results indicated that the Chen-Kao test was useful for exclusion of cathinones. A combination of the modified Scott test and the Chen-Kao test was successfully applied to the forensic samples containing cocaine or pyrrolidine-type cathinones. In conclusion, a combination of these tests will be the useful field-test procedure for cocaine. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Hair and nails are often used to prove drug intake over several months. However, it is impossible to determine the day of drug intake by conventional segmental analysis of bulk samples. To improve this segmental analysis, we prepared accurate 0.4-mm hair and 0.2-mm nail segments, which correspond to their respective growth rates of 1-2 days, using a tissue slicer. The aim of this study was to develop an efficient method to extract drugs from a single sub-millimeter segment of hair and nail. Hair and nails were collected from a subject who was administered a single dose of chlorpheniramine. Four drug extraction methods based on different principles such as sonication, microwaves, micropulverization, and alkaline dissolution were compared. Short-duration sonication followed by long-duration soaking served the aim. Drug extraction from a sub-millimeter segment was performed in three steps as follows: a segment was first washed, followed by sonication for 10 min soaking in the extraction solution for 24 h. The drug concentrations in the three extracts from each segment were quantified using high performance liquid chromatography-tandem mass spectrometry. Each concentration was displayed on a single hair strand and a single nail block so that the first, second, and third extracts corresponded to components on the surface, in the outer layer, and within the sample, respectively. The distribution of chlorpheniramine in a hair successfully reflected the intake history. This method can be used in the future to measure the detailed distribution of drugs in a single hair and nail. (C) 2016 Elsevier B.V. All rights reserved.

We developed a novel immunoassay for herbal cannabis based on a new immunoassay principle that uses Ultra Quenchbody ("UQ-body"), a recombinant antibody Fab fragment fluorolabeled at the N-terminal regions. When the antigen binds to anti-Delta(9)-tetrahydrocannabinol (THC) UQ-body, the fluorescence intensity (FI) decreases. The analytical conditions of the immunoassay were optimized based on the FI reduction rate (FIRR). Following are the steps in the final analytical procedure: (1) 10 mg of samples were extracted with 1 ml of a 60:40 mixture of methanol and phosphate-buffered saline (PBS); (2) the extract was filtered through a centrifugal 0.2-mu m polytetrafluoroethylene membrane filter; (3) the filtrate was diluted 100 times with extraction solvent; (4) 6-mu l diluted solution was mixed with 19-mu l PBS and 75-mu l ml UQ-body solution; and (5) FIRR was measured under 275-mV excitation light. Herbal cannabis samples containing >= 4.0-mg/g THC gave FIRRs of >= 5.2%. FIRRs of negative samples (cigarette, tea, spice, and so-called "synthetic marijuana") were <= 3.1%. When setting the FIRR threshold to 5.0%, cannabis samples containing >= 4.0-mg/g THC were correctly judged as positive without being affected by false positives caused by the negative samples. This detection limit was lower than total THC level (10-200 mg/g) in most herbal cannabis samples seized in Japan. In seven of the 10 cannabis samples, the results of the UQ-body test were comparable with those of the Duquenois-Levine test. Thus, the UQ-body-based immunoassay is presumed to be an effective and objective drug screening method for herbal cannabis; however, to show the true usefulness, it is necessary to test a number of real case samples in the field situation. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

This is the first report on development of a library search-based screening system for 3,4-methylenedioxymethamphetamine (MDMA) in ecstasy tablets using a portable near-infrared (NIR) spectrometer. The spectrum library consisted of spectra originating from standard substances as well as mixtures of MDMA hydrochloride (MDMA-HCl) and diluents. The raw NIR spectra were mathematically pretreated, and then, a library search was performed using correlation coefficient. To enhance the discrimination ability, the wavelength used for the library search was limited. Mixtures of MDMA-HCl and diluents were used to decide criteria to judge MDMA-positive or MDMA-negative. Confiscated MDMA tablets and medicinal tablets were used for performance check of the criteria. Twenty-two of 27 MDMA tablets were truly judged as MDMA-positive. Five false-negative results may be caused by compounds not included in the library. No false-positive results were obtained for medicinal tablets. This system will be a useful tool for on-site screening of MDMA tablets.

In forensic drug testing, it is important to immediately take biological specimens from suspects and victims to prove their drug intake. We evaluated the effectiveness of saliva and fingerprints as alternative specimens to urine and blood in terms of ease of sampling, drug detection sensitivity, and drug detection periods for each specimen type. After four commercially available pharmaceutical products were administered to healthy subjects, each in a single dose, their urine, blood, saliva, and fingerprints were taken at predetermined sampling times over approximately fourweeks. Fourteen analytes (the administered drugs and their main metabolites) were extracted from each specimen using simple pretreatments, such as dilution and deproteinization, and were analyzed using liquid chromatography/mass spectrometry (LC/MS). Most of the analytes were detected in saliva and fingerprints, as well as in urine and blood. The time-courses of drug concentrations were similar between urine and fingerprints, and between blood and saliva. Compared to the other compounds, the acidic compounds, for example ibuprofen, acetylsalicylic acid, were more difficult to detect in all specimens. Acetaminophen, dihydrocodeine, and methylephedrine were detected in fingerprints at later sampling times than in urine. However, a relationship between the drug structures and their detection periods in each specimenwas not found. Saliva and fingerprints could be easily sampled on sitewithout using special techniques or facilities. In addition, fingerprints could be immediately analyzed after simple and rapid treatment. In cases where it would be difficult to immediately obtain urine and blood, saliva and fingerprints could be effective alternative specimens for drug testing. Copyright (C) 2015 John Wiley & Sons, Ltd.

The urinary metabolic profiles of three hallucinogenic 2,5-dimethoxy-4-alkylthiophenethylamine analogs: 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2), 2,5-dimethoxy-4-isopropylthiophenethylamine (2C-T-4), and 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), were investigated in rats. For each drug, four male Sprague-Dawley rats were orally administered 10 mg/kg of 2C-T-2, 2C-T-4, or 2C-T-7, and urine was collected 0-24 and 24-48 h after administration. The urine samples were processed by liquid-liquid extraction, and the extracts were analyzed by liquid chromatography/mass spectrometry to quantify the metabolites. The metabolic patterns of these drugs were different: for 2C-T-7, the principal metabolite was the beta-hydroxylated-N-acetylated-sulfoxide, whereas for 2C-T-2 and 2C-T-4 the major metabolites were the N-acetylated-sulfoxide and S-methylated-N-acetylated-sulfoxide, respectively.

The influences of typical methods for visualization and sampling of fingerprints on drug detection in latent fingerprints were examined and the feasibility of drug detection in a practical crime scene was evaluated. After fexofenadine, chlorpheniramine, and acetaminophen were spotted on drug-free latent fingerprints formed on various materials such as stainless steel, plastic, and glass, the drugs were extracted from the fingerprints using various methods. In all the drugs, the extraction by pipetting on a latent fingerprint (direct extraction method) yielded higher recovery rates than the extraction by pipetting on an adhesive tape with a latent fingerprint (transfer and extraction method). There were little influences of powder for fingerprint visualization for the recovery of drugs in the direct extraction method. Some of the combination between drugs and materials with fingerprints reduced the recovery rates in the transfer and extraction method. The drug analysis in latent fingerprints on paper was not practical in terms of the handling of drug extraction and the recovery of drugs. Based on a supposition of a practical crime scene, latent fingerprints after drug administration were taken using typical methods for visualization and sampling of fingerprints. Some drugs were detected from latent fingerprints even in case of drug administration at their single doses and even after the fingerprints and the adhesive tapes were stored for one week. Moreover, the detection of nicotine and its metabolite, cotinine, in latent fingerprints was effective to judge whether the person with the fingerprint was a smoker or not. Drug detection in latent fingerprints would be useful to elucidate the relationship between a specific person and drugs in criminal investigation.<br>

A method to distinguish the presence or absence of relationship between two cannabis seizures is required for forensic investigations. In this study, we focused on the chemical profile of the cannabis. We developed a method to discriminate whether the two cannabis seizures derived from a single organism or different ones ("individual" discrimination) and whether the two seizures had been seized in the same criminal investigation or not ("case" discrimination). Discrimination ability of these methods were evaluated statistically.  For 21 cannabis seizures, gas chromatography/time-of-flight mass spectrometry analysis were conducted to obtain the comprehensive chemical profile. The contents of not only cannabinoids and terpenes but almost all detected compounds were used as variables to perform multivariate analysis. Using hierarchical cluster analysis, most of the cannabis seized in an identical case formed one group in the dendrogram. The cannabis cultivated outdoors and indoors belonged to different groups.  441 hierarchical cluster analysis were performed with a combination of all pair of cannabis seizures to calculate the Euclidean distance between specimens based on definite rules. Two thresholds were arbitrarily set for the distance to perform two types of cannabis discrimination. The equal error rate and the area under the receiver operating characteristic curve of "individual" discrimination were 0.024 and 0.997 and those of "case" discrimination were 0.220 and 0.867. By selecting an appropriate threshold, "individual" discrimination was achieved with sensitivity of 0.810, specificity of 0.998 and accuracy rate of 0.989. Similarly, "case" discrimination was with sensitivity of 0.627, specificity of 0.971 and accuracy rate of 0.925. These results suggested that the present method by using hierarchical cluster analysis of chemical profile would be effective for cannabis discrimination in forensic investigations.

There has been a rapid increase over the last decade in the appearance of new non-controlled psychoactive substances. Minor changes in the chemical structures of these compounds, such as the extension of an alkyl residue or replacement of a single substituent, are regularly made to avoid regulatory control, leading to the manufacture of many new potentially dangerous drugs. Bromoamphetamine analogs (bromoamphetamine [Br-AP] and bromomethamphetamine (Br-MA]) are ring-substituted amphetamines that can behave as stimulants, as well as exhibiting inhibitory activity towards monoamine oxidases in the same way as amphetamines. Gas chromatography-tandem mass spectrometry (GC-MS-MS) was used in this study to differentiate ring-substituted bromoamphetamine analogs. Free bases, trifluoroacetyl derivatives, and trimethylsilyl (TMS) derivatives of six analytes were successfully separated using DB-1ms and DB-5ms columns. Electron ionization MS-MS analysis of the TMS derivatives allowed for the differentiation of three regioisomers. TMS derivatives of 2-positional isomers provided significant product ions. The spectral patterns of 3- and 4-positional isomers were different. Chemical ionization MS-MS analysis of free bases for [M+H-HBr](+) ions at m/z 134 and 148 allowed for differentiation of the regioisomers. The spectra of 2-positional isomers contained characteristic product ions formed by dehydrogenation at m/z 132 and m/z 146 for 2Br-AP and 2Br-MA, respectively. The spectra of 3-positional isomers contained alpha-cleaved iminium cations as the base peaks. The spectra of 4-positional isomers showed a tropylium cation at m/z 91 as the base peak. These results demonstrate that GC-MS-MS can be used for the differentiation of regioisomeric Br-AP analogs in forensic practice.

In recent years, a large number of clandestinely synthesized new psychoactive substances with high structural variety have been detected in forensic samples. Analytical differentiation of regioisomers is a significant issue in forensic drug analysis, because, in most cases, legal controls are placed on only one or two of the conceivable isomers. In this study, gas chromatography-tandem mass spectrometry (GC-MS-MS) was used to differentiate the regioisomers of chloroamphetamine analogs (chloroamphetamines and chloromethamphetamines) synthesized in the authors' laboratories. Free bases, trifluoroacetyl derivatives, and trimethylsilyl derivatives were subjected to GC-MS-MS using DB-1ms, DB-5ms, and DB-17ms capillary columns, respectively. The regioisomers of chloroamphetamine analogs in all forms were well separated on the DB-5ms column. The electron ionization mass spectra of the chloroamphetamine analogs gave very little structural information for differentiation among these analogs, even after trifluoroacetyl and trimethylsilyl derivatization of the analytes. Characteristic product ions of the 2-positional isomers were observed by electron ionization-MS-MS. In contrast, chemical ionization-MS-MS of the free bases provided more structural information about chloride position on the aromatic ring when [M+H-HCl](+) was selected as a precursor ion. The results suggest that a combination of chromatographic analysis and MS-MS supports differentiation for regioisomers of chloroamphetamine analogs.

We observed the decomposition of the hydrochloride salt of alpha-pyrrolidinoheptanophenone (alpha-PHPP-HCl), a newly distributed pyrrolidine-type cathinone derivative when 2.5 ng of this substance was placed in glass test tubes and stored in a refrigerator for 3 days. To further investigate this phenomenon, we studied the (i) time course of the residual ratios of alpha-PHPP-HCl when a small amount (10 mu g) of alpha-PHPP-HCl was stored in glass vials in air at room temperature; (ii) identification of the decomposition products of alpha-PHPP-HCl; (iii) effect of air on the decomposition process; (iv) effect of the added amounts of alpha-PHPP-HCl on its decomposition; and (v) comparison of the stability between various cathinone derivatives and their decomposition products. The decomposition of alpha-PHPP-HCl occurred in air and increased with time. Two possible decomposition products, alpha-(2 ''-oxopyrrolidino)heptanophenone and alpha-PHPP-N-oxide, were identified. These products were formed by oxygen in air because the yield significantly decreased by storing them in a vacuum desiccator. With the decrease in the amount of alpha-PHPP-HCl, the residual ratios decreased and amount of the decomposition products increased. This indicates that the decomposition of alpha-PHPP-HCl occurred on the upper surface of the samples. The hydrochloride salts of other cathinone derivatives were also unstable in air, and the residual ratios observed were different depending on the compounds. The pyrrolidine-type cathinone derivatives afforded two types of decomposition products, which were presumed to be 2 ''-oxo and N-oxide derivatives, similar to alpha-PHPP-HCl. In contrast, secondary amine-type cathinone derivatives showed different decomposition patterns, possibly including the dealkylated derivative. These findings may be very useful for the future toxicological analysis of cathinone derivatives. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Abuses of new psychoactive substances have recently become serious social problems. When synthetic cannabinoids are consumed, most of the drugs are not detected in unchanged form from the urine. In that cases, it is difficult to determine what drug was consumed in drug testing. If blood and saliva of suspects are obtained immediately after drug consumption, unchanged drugs could be detected from the specimens. Therefore, on-site sampling of these specimens are effective to determine the consumed drugs. We examined how police officers easily obtain blood and saliva of suspects on site and what drug concentrations are needed to detect drugs in blood and saliva obtained by the sampling methods. First, blood and saliva sampling methods were examined using various collecting tools. For blood sampling method, it was effective to bleed from a fingertip with a lancet and then to absorb the blood to paper pulp. Blood of approximately 5 μL was obtained by this safe and simple method. For saliva sampling method, dropping saliva directly into a 25 mL centrifuge tube (direct sampling method) was convenient for drug analysts. However, because some subjects felt it unpleasant that the sampling situation was watched by the observer, the alternative sampling method, absorbing saliva in a mouth with a cotton swab was also used. Saliva of at least 50 μL was obtained by the two methods. Next, five drugs (JWH 018, 5F-APINACA, 4-MeO α-PVP, 4-Cl AMP and MeBP) in blood and saliva were analyzed using a liquid chromatograph-ion trap mass spectrometer to estimate the concentrations required for drug detection. The limits of detection of five drugs were in the range of 0.1-10 ng/mL for blood (5 μL) and 0.01-1 ng/mL for saliva (50 μL) obtained by the direct sampling method. On the other hand, absorbing saliva by a swab made drug detection difficult because synthetic cannabinoids, JWH 018 and 5F-APINACA, were strongly adsorbed in the swab. It is considered that saliva obtained by the direct sampling method is effective for drug testing because the sampling is rapid and simple, a large volume of saliva is obtained, and the drug concentrations in abusers' saliva are generally high as compared with those in blood.<br>

A portable near infrared spectrometer was applied to the presumptive identification of psychotropic drugs based on library searching. Data-treatment methods (mathematical pretreatment and library search algorithm) were examined on the basis of differentiation ability. The optimized mathematical pretreatment was a standard normal variate followed by the 2nd derivative. The correlation coefficient showed the best differentiation ability in the library search algorithms. Optimized data-treatment was effective for minimizing the effect of particle size on identification. The optimized data-treatment methods were validated by the spectra of psychotropic substances (n = 120). Identification criteria for the psychotropic drugs were decided on the basis of the results of the validation. As a consequence, 8 out of 11 forensic samples containing psychoactive substances were able to be positively identified. Thus, the portable near infrared spectrometer with optimized data-treatment processing is a useful tool for rapid screening and presumptive identification of seized materials. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

We evaluated whether a fingerprint, which consists of secretions from the fingertips, is a suitable biological sample for drug testing. A commercially available cold medicine containing ibuprofen, dihydrocodeine, chlorpheniramine, and methylephedrine was administered to healthy subjects. The subjects washed their hands with tap water and hand soap to remove the external contaminants, and then pressed a fingertip onto wet filter paper at fixed sampling times (from 2 h to 7 days). The analytes on the filter paper were dissolved in 25 % methanol-water, and a large volume (50 mu l) of the extract was analyzed by liquid chromatography-tandem mass spectrometry. The relationship between the sampling times and the concentration of analytes in fingerprints was examined. The results were compared with drug concentrations in blood samples. Most of the drugs and their metabolites were detected from fingerprints at 7 days after drug administration. The fingerprint sample preparation is rapid (ca. 3 min) and simple, and the limits of detection were 0.1 pg/fingerprint for dihydrocodeine, chlorpheniramine, and methylephedrine. We demonstrate that drugs can be detected in fingerprints at later sampling times with more rapid and simpler sample preparation than in blood. The method should be applicable to drug testing in criminal investigations.

Quinolin-8-yl 1-pentyl-(1H-indole)-3-carboxylate (QUPIC) is a newly introduced synthetic cannabinoid in the drug market. This drug was found to undergo thermal decomposition during gas chromatography-mass spectrometry (GC-MS), probably because of the presence of an ester bond in its structure. Most notably, when QUPIC dissolved in methanol or ethanol was analyzed by GC-MS, most of the QUPIC decomposed to give thermal degradation products. We identified the products as methyl 1-pentyl-(1H-indole)-3-carboxylate, ethyl 1-pentyl-(1H-indole)-3-carboxylate, and methyl indole-3-carboxylate by comparison of their mass spectra with those of reference standards synthesized in our laboratory. Nonalcoholic solvents such as acetone and chloroform gave a major peak and a minor peak for unchanged QUPIC and the degradation product 8-quinolinol, respectively. Furthermore, we studied the effects of various parameters, such as injection methods (splitless or split, and split ratio), injector temperatures, and injector liners on the thermal degradation of QUPIC. Split injection was effective in avoiding degradation. When performing splitless injection, an injector temperature of 250 A degrees C and a surface deactivated injector liner without glass wool minimized the degradation and enhanced the sensitivity. These results indicate that special attention is required for GC-MS analysis of QUPIC, and the information presented in this study will be very useful for forensic toxicologists using GC-MS.

Herb mixtures including cannabis among the other herbs have recently appeared. When cannabinoids from herb extracts are detected by chemical examinations such as gas chromatography/mass spectrometry, forensic analysts have to determine whether cannabis is actually in the mixture or the cannabinoids are spiked. Morphological examinations are time-consuming, since it is difficult to find several pieces of cannabis among a large number of herb pieces using a microscope. Here, we propose a procedure for efficiently searching for cannabis in herb mixtures using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI/IMS). Pieces of herb mixtures were spread on double-sided adhesive tape attached to a stainless steel plate. The pieces were then covered with a conductive sheet and pressed. After a solution containing a matrix reagent was sprayed, the distribution of cannabinoids in the sample was visualized by MALDI/IMS. Then, just the pieces with cannabinoids could be picked up selectively with tweezers and decolorized. Cystolith hairs and trichomes, which are characteristic of cannabis, were observed in most of these pieces using a biological microscope. This MALDI/IMS procedure enables cannabis to be found in herb mixtures without inefficient random sampling and microscopic morphological examination.

We review our studies of drug profiling of methamphetamine, the most abused drug in Japan, in this article. Drug profile was defined as a set of specific characteristics selected to provide information on the drug sources and histories, such as starting materials, synthetic routes and clandestine manufacturing. We developed a method for methamphetamine impurity-profiling using capillary gas chromatography. Impurities were extracted from methamphetamine hydrochloride with an organic solvent under alkaline conditions, and detected very well with good resolution. Using four internal standards improved the correction of retention times for inter-day or inter-laboratory comparisons of chromatograms. We also investigated the simultaneous chiral separation of 9 amphetamine-type stimulants that include methamphetamine and the precursors by capillary electrophoresis. The enantiomers were well resolved, and small peaks of the precursor impurities (i.e. ephedrines) of methamphetamine were detectable by analyzing the solution. We also investigated an evaluation method for linking MA seizures using stable isotope ratio mass spectrometry, and the usefulness of crystal-level profiling analysis was shown. Combining the several analyses revealed detail drug profiles, and enabled to acquire much more information on linking or discriminating seizures as well as the clandestine manufacturing of the drug.

In recent years, a large number of tryptamine-based designer drugs have been encountered in forensic samples. We have developed simultaneous analytical methods for 14 tryptamine analogues using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS). Trimethylsilyl (TMS) derivatives of the analytes were separated on a DB-1ms column within 15 min. The structural isomers could be differentiated by electron ionization GC-MS. LC-MS-MS with a C-18 column could separate structural isomers of tryptamines except for a combination of 5-methoxy-N,N-diethyltryptamine and 5-methoxy-N-methyl-N-isopropyltryptamine. Higher collision energy gave different product ion spectra between the structural isomers. The results indicate that GC-MS is the first choice for identification of tryptamines, preferably after TMS derivatization, and LC-MS-MS can be used as a complementary approach for the unequivocal differentiation of tryptamine isomers.

alpha-Pyrrolidinopentiophenone (alpha-PVP) is a popular recreational drug in Japan. This drug easily undergoes thermal decomposition during gas chromatography/mass spectrometry analysis. We evaluated three factors involved in the decomposition, namely the injection method (splitless or split, split ratio), injector temperature, and surface activity on the inlet liner. Splitless injection of alpha-PVP using a used deactivated split/splitless liner at an injector temperature of 250 degrees C caused thermal decomposition. This decomposition was inhibited by split injection. A higher split ratio resulted in greater prevention. Based on the mass spectrum of deuterated alpha-PVP, the decomposition product was presumed to be an enamine whose double bond was located in the alkyl chain. Lowering the injection temperature from 250 degrees C to 200 degrees C did not prevent decomposition. New glass liners, both deactivated and non-deactivated, were compared. The use of a new deactivated liner minimized thermal decomposition, even for splitless injection, while the non-deactivated liner generated an increase in the amount of the decomposition product. These results showed that the injection method and the surface activity on the inlet liner were involved in the thermal decomposition of alpha-PVP. (c) 2013 Elsevier Ireland Ltd. All rights reserved.

The present study has attempted to downscale a mass spectrometer in order to make it portable and enable onsite analysis with it. The development of a small mass spectrometer required the use of a compact pump whose displacement was small, decreasing the sensitivity of that spectrometer. To get high sensitivity with a small mass spectrometer, we have integrated novel techniques: a highly sensitive ionization source and efficient extraction of sample vapor. The low-pressure dielectric barrier discharge ionization (LP-DBDI) source made it possible to increase the conductance between the source and the mass analyzer, compared with ambient ionization sources, enhancing the efficiency of the ion transfer from the ionization source to the mass analyzer. We have also developed a vacuumed headspace method efficiently transporting the sample vapor to the ionization source. The sensitivity was further enhanced by also using a discontinuous sample gas introduction technique. A prototype portable mass spectrometer using those novel techniques was found to be sensitive enough to detect 0.1 ppm methamphetamine, 1 ppm amphetamine, 1 ppm 3,4- methylenedioxymethamphetamine, and 10 ppm cocaine in liquid. © 2013 American Chemical Society.