Gamma hydroxybutyric acid (GHB) concentrations in humans and factors affecting endogenous production

The endogenous nature of the drug of abuse gamma hydroxybutyric acid (GHB) has caused various interpretative problems for toxicologists. In order to obtain data for the presence of endogenous GHB in humans and to investigate any factors that may affect this, a volunteer study was undertaken. The GHB concentrations in 119 urine specimens from GHB-free subjects and 25 urine specimens submitted for toxicological analysis showed maximal urinary GHB concentrations of 3mg/l. Analysis of 15 plasma specimens submitted for toxicological analysis detected no measurable GHB (less than 2.5mg/l). Studies in a male and female volunteer in which different dietary food groups were ingested at weekly intervals, showed significant creatinine-independent intra-individual fluctuation with overall urine GHB concentrations between 0 and 2.55, and 0 and 2.74mg/l, respectively. Urinary concentrations did not appear to be affected by the particular dietary groups studied.The concentrations measured by gas chromatography with flame ionisation detection (GC-FID) and gas chromatography with mass spectrometry (GC-MS) lend further support to the proposed urinary and plasma interpretative cut-offs of 10 and 4mg/l, respectively, where below this it is not possible to determine whether any GHB detected is endogenous or exogenous in nature.     

Analysis of 4‐Bromo‐2,5‐DimethoxyphenethylamineAbuser's Urine: Identification and Quantitation of Urinary Metabolites

The metabolites of 4‐bromo‐2,5‐dimethoxyphenethylamine (2C‐B), a psychoactive drug with hallucinogenic activity, were investigated in a urine sample from a user of 2C‐B. The urine sample was deconjugated enzymatically and the metabolites were recovered by liquid–liquid extraction. The extract was analyzed by gas chromatography/mass spectrometry after derivatization, and the results were used to identify and quantitate the metabolites. 4‐Bromo‐2,5‐dimethoxyphenylacetic acid was the most abundant metabolite of 2C‐B in human urine and accounted for 73% of the total amount of detected metabolites, followed by 4‐bromo‐2‐hydroxy‐5‐methoxyphenylacetic acid (13%) and 4‐bromo‐2,5‐dimethoxyphenylethyl alcohol (4.5%). According to the literature, the main metabolites of 2C‐B in rat urine are N‐(4‐bromo‐2‐methoxy‐5‐hydroxyphenylethyl)acetamide and N‐(4‐bromo‐2‐hydroxy‐5‐methoxyphenylethyl)acetamide. However, these metabolites accounted for only a small proportion of the total amount of detected metabolites in human urine, which indicates that there are significant species‐specific differences in the metabolism of 2C‐B. 4‐Bromo‐2,5‐dimethoxyphenylacetic acid, which was the most abundant metabolite in human urine, is thought to be generated by deamination of 2C‐B by monoamine oxidase (MAO) followed by oxidation by aldehyde dehydrogenase. Our results suggest that MAO plays a crucial role in the metabolism of 2C‐B in humans.     

合成大麻素类新精神活性物质AB-CHMINACA的体内与体外代谢研究

目的 通过UPLC-HRMS检测分析体外人肝微粒体模型中合成大麻素类新精神活性物质AB-CHMINACA的代谢物并与一例真实滥用者的尿液样本进行对比,从而对体外人肝微粒体模型预测体内代谢物的一致性进行评价研究.方法 通过建立体外人肝微粒体孵育模型模拟人体体内代谢过程,尿液样本经简单的乙腈沉淀蛋白后利用高分辨质谱(HRM...     

Intoxication due to 1,4-butanediol

We report a case of intoxication resulting from the ingestion of a liquid, sold in the illicit market as "liquid ecstasy," which was found to contain 1,4-butanediol, a metabolic precursor of gamma-hydroxybutiric acid (GHB). Identification of the substance in the liquid was performed by gas chromatography-mass spectrometry (GC-MS).The toxicological analysis of blood, urine and gastric content of the victim was performed by immunoassay and gas chromatography with nitrogen-phosphorus detection as screening techniques and by means of GC-MS for confirmation and quantitation of 1,4-butanediol and GHB. The following drug concentrations were found: 82 microg/ml (blood), 401 microg/ml (urine) and 7.4 microg/ml (gastric content) for 1,4-butanediol and 103 microg/ml (blood), 430.0 microg/ml (urine) for GHB. In addition to these, other drugs detected and their blood concentration found in this case were methylenedioxymethylamphetamine (MDMA) 0.23 microg/ml and its metabolite methylenedioxyphenylamphetamine (MDA) 0.10 microg/ml. In the urine, a concentration of 0.10 microg/ml of benzoylecgonine was also found.     

Toxicological Analysis of Opiates from Alternative Matrices Collected from an Exhumed Body

In this case study, the body of a 45‐year‐old man was exhumed after 1 year at the request of the public prosecutor to assess whether the death was caused by drug consumption. Toxicological analyses were performed on several matrices, including liver, kidney, and the alternative matrices hair and teeth. The systematic toxicological analysis (STA), which consisted of basic and acid liquid/liquid extraction and gas chromatography–mass spectrometry (GC‐MS) analysis, showed the presence of opiates in each of the matrices analyzed. Subsequently, to confirm and quantify the presence of opioids, samples of each of the matrices were subjected to solid‐phase extraction and specific GC‐MS analysis. The case presented demonstrates the possibility of drug detection in an exhumed body that has been buried for 1 year, despite the problems of quantitative interpretation of the data, and that toxicological results could be useful along with other forensic evidence.     

Systematic Toxicological Analysis Revealing a Rare Case of Captan Ingestion

This article presents a case of suicide by intoxication with various pharmaceuticals, particularly anticonvulsants, combined with the fungicide captan. A cause of death could not be ascertained at autopsy. However, systematic toxicological analysis (STA) including a screening via solid‐phase microextraction (SPME) and gas chromatography‐mass spectrometry (GC‐MS) for (semi) volatile organic compounds revealed results suggesting a possible cause of death. The effects of captan on the human organism, its metabolism, and distribution will be discussed. Macroscopically, the cause of death was unascertained. STA revealed clonazepam, citalopram, and its metabolites, lamotrigine, levetiracetam, lacosamide, clonazepam, captan, and its metabolite tetrahydrophthalimide (THPI). For the first time, it was detected in human viscera. A quantification of THPI was performed to obtain distribution in the organs. The significance of a complete STA must be emphasized. The presence of THPI would have been missed without previous detection of captan. Consequently, this fatality would not have been investigated satisfactorily.     

Changed compounds of hydroxyzine in a human urine

During a forensic toxicological GC/MS screening, changed compounds of hydroxyzine were found in a man's urine taken about 20 h after ingesting sake (Japanese liquor) and tranquilizers. The structures of those compounds were assigned to 4-chlorodiphenylmethane(I), p-chlorbenzophenone(III), norchlorcyclizine(IV), 7-(p-chloro-alpha-phenylbenzyl)-2-hydroxy-2H,3H-oxazolo-[3,2 -alpha] piperazine(V), 1-(p-chloro-alpha-phenylbenzyl)-4-methylpiperazine-3-one(VI), N-(p-chloro-alpha-phenylbenzyl)-N'-formylmethyl-N'- hydroxyethyl-1,2-ethenediamine(VII) and 1-(p-chloro-alpha-phenylbenzyl)-4-[2-ethoxy(2-ethoxy)-ethyl] piperazine(VIII) on the basis of the fragmentation patterns and relative retention times except VIII which was identified using the synthesized compound. I, V, VI, VII and VIII have not been reported previously, but the possibility of metabolites of hydroxyzine is still uncertain.     

Fatal tolperisone poisoning: autopsy and toxicology findings in three suicide cases

Tolperisone (Mydocalm) is a centrally acting muscle relaxant with few sedative side effects that is used for the treatment of chronic pain conditions. We describe three cases of suicidal tolperisone poisoning in three healthy young subjects in the years 2006, 2008 and 2009. In all cases, macroscopic and microscopic autopsy findings did not reveal the cause of death. Systematic toxicological analysis (STA) including immunological tests, screening for volatile substances and blood, urine and gastric content screening by GC-MS and HPLC-DAD demonstrated the presence of tolperisone in all cases. In addition to tolperisone, only the analgesics paracetamol (acetaminophen), ibuprofen and naproxen could be detected. The blood ethanol concentrations were all lower than 0.10 g/kg. Tolperisone was extracted by liquid-liquid extraction using n-chlorobutane as the extraction solvent. The quantification was performed by GC-NPD analysis of blood, urine and gastric content. Tolperisone concentrations of 7.0 mg/l, 14 mg/l and 19 mg/l were found in the blood of the deceased. In the absence of other autopsy findings, the deaths in these three cases were finally explained as a result of lethal tolperisone ingestion. To the best of our knowledge, these three cases are the first reported cases of suicidal tolperisone poisonings.     

Disappearance of cocaine from human hair after abstinence

In this work the study of the disappearance of cocaine in hair is reported. The subject of the study is a woman who stopped the consumption of cocaine after a period of drug abuse of over 1 year. Hair samples were collected over a period of 10 months. During this time the absence of cocaine intake was monitored by the toxicological analysis of urine, performed every 2 days. After decontamination with methanol, the hair sample, cut in two segments (0-1.5 and 1.5-3 cm from the hair root) was added with cocaine-D(3) (internal standard), hydrolyzed and extracted with chloroform/isopropanol (9:1). The extract was evaporated to dryness, reconstituted in 25 microl of ethyl acetate and analyzed by GC-MS in SIM mode. The obtained results show that the incorporation of cocaine in hair decreased during the first 3 months after the last consumption and after this period of time no cocaine was found in the hair sections closest to the root.     

Fatal intoxication involving 2-methyl AP-237

Novel synthetic opioids contribute considerably to the opioid epidemic, especially with the frequent emergence of structurally similar compounds. This case report describes a fatal intoxication involving 2-methyl AP-237. A 54-year-old Caucasian male was found deceased from an apparent drug overdose. A plastic container labeled “2MAP” and a cut straw were found in the decedent's backpack at the scene. A white substance found in the container tested positive for fentanyl by field testing. According to his medical history, the decedent was treated for a drug overdose 3 years prior to his death. With no diagnostic findings at autopsy, the case was submitted for toxicological analysis. An unknown substance was detected in peripheral blood and urine using gas chromatography with nitrogen phosphorous detection (GC-NPD). Further testing was conducted using gas chromatography–mass spectrometry (GC–MS) and liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) which confirmed the presence of 2-methyl AP-237 and potential metabolites in blood and urine. Quantitation by GC-NPD revealed concentrations of 2-methyl AP-237 in blood and urine at 480 ng/mL and 4200 ng/mL, respectively. The toxicological analysis also identified and quantitated alprazolam in the blood at 55 ng/mL. Additionally, the metabolism of 2-methyl AP-237 was investigated and three hydroxylated metabolites were identified in peripheral blood and urine. Limited literature is available for the detection and quantitation of 2-methyl AP-237 in postmortem specimens. Given the toxicological findings with unremarkable autopsy findings, this case is an example of a fatal intoxication involving 2-methyl AP-237.     

The designer drug situation in Ibiza

A total of 137 urine samples and 46 serum samples, corresponding to 154 self-confessed designer drugs consumers in Ibiza island, were analyzed for the presence of designer drugs: amphetamine and amphetamine derivatives (methamphetamine, methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), methylenedioxyamphetamine (MDA), p-methoxymethylamphetamine (PMMA), p-methoxyamphetamine (PMA), etc.), ketamine and gamma-hydroxybutyric acid. Among this population, coming both from the forensic clinic and from the emergency room of a hospital, a total of 99 cases were found positive for some designer drug. This study shows the prevalence of methylenedioxymethamphetamine (MDMA) among designer drug users, sole or in association with other drugs. Also, the mixture of MDMA with other designer drugs, ethanol and/or cocaine is shown to be more likely to produce toxic symptoms requiring clinical attendance in a hospital emergency room. These findings along with the consumption history, the concentrations of drugs and metabolites in urine and serum and the toxicological significance for the interpretation of some MDMA metabolites such as 4-hydroxy-3-methoxymethamphetamine (HMMA) are discussed in this study.     

Metabolites of ephedrines in human urine after administration of a single therapeutic dose

Ephedrine (EPH), pseudoephedrine (PEPH), phenylpropanolamine (PPA), methylephedrine (MEPH) and cathine are sympathomimetic amines. These drugs are commonly found in over-the-counter (OTC) cold medicines and some dietary supplements. In Taiwan, the misuse of these drugs has resulted in an increase in athletic violations. Excretion studies of the ephedrine-related drugs have been performed to better understand the metabolic yields of ephedrines in urine. After consuming a single clinical dose of each of these drugs, urine samples from volunteers (n=3 for each drug) were subjected to tert-butyl-methyl-ether (TBME) extraction and trifluoroacetic acid (TFAA) derivatization before gas chromatography-mass spectrometry (GC-MS) analysis. Most ephedrines were excreted unchanged in urine, including EPH (40.9%), PEPH (72.2%), and PPA (59.3%). However, only a relatively small amount of MEPH (15.5%) was excreted unchanged in urine. In addition, a trace amount of PPA (1.6%) and cathine (0.7%) was found to be the metabolites of EPH and PEPH, respectively. Urinary EPH, PEPH, and PPA reached peaks at 2-6h and disappeared in urine at approximately 24-48 h post-administration. For MEPH, the peaks of excretion extended from 4 to 12h post-administration and were undetectable at approximately 48 h. A single clinical dose of EPH (25 mg) may exceed threshold level (10 microg/mL) in sport drug testing if the urine samples are tested within approximately 8h post-administration. However, a single dose of MEPH (20 mg) never reached the threshold value (10 microg/mL).     

The GC/MS analysis of some commonly used non-steriodal anti-inflammatory drugs (NSAIDs) in pharmaceutical dosage forms and in urine

All the commonly used non-steriodal anti-inflammatory drugs (NSAIDs), except mefenamic acid, when extracted from the pharmaceutical dosage forms or the urines of users, and derivatized by silylation and then analysed by GC/MS, gave the mono- or the di-trimethylsilyl derivatives (depending on the number of derivatized groups in the drug) as the sole products. Mefenamic acid gave a mixture of products. When extracted from pharmaceutical dosage froms or from the urines of users, and analysed by GC/MS without derivatization, some of the NSAIDs were separated and detected as the unchanged molecules as the sole products, while others were separated and detected in altered forms as sole products or mixtures, depending on: (a) the solvent in which the extract was dissolved for injection into GC/MS, (b) the chemical structure of the drug, and (c) specifically for diflunisal, the presence or absence of potential methylating and/or acetylating agents on the GC column and/or septum. The main thermally-induced reactions of the underivatized NSAIDs included (i) methyl ester formation at the COOH group when the extract was dissolved in methanol, (ii) decarboxylation (i.e., loss of CO2), (iii) dehydration (i.e., loss of H2O) when the chemical structure permitted, such as for diclofenac, and (iv) cleavage at a carbon-heterocyclic nitrogen bond when one is present in an NSAID. Heating the urine in approximately 2 M HCl at 100 degrees C for 30 min, has been found to be a satisfactory means for effecting hydrolysis of the NSAIDs glucuronide conjugates. No metabolites, resulting from aromatic-ring hydroxylation, have been detected in urine for any of the NSAIDs studied.     

The designer drug situation in Ibiza

A total of 137 urine samples and 46 serum samples, corresponding to 154 self-confessed designer drugs consumers in Ibiza island, were analyzed for the presence of designer drugs: amphetamine and amphetamine derivatives (methamphetamine, methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), methylenedioxyamphetamine (MDA), p-methoxymethylamphetamine (PMMA), p-methoxyamphetamine (PMA), etc.), ketamine and γ-hydroxybutyric acid. Among this population, coming both from the forensic clinic and from the emergency room of a hospital, a total of 99 cases were found positive for some designer drug. This study shows the prevalence of methylenedioxymethamphetamine (MDMA) among designer drug users, sole or in association with other drugs. Also, the mixture of MDMA with other designer drugs, ethanol and/or cocaine is shown to be more likely to produce toxic symptoms requiring clinical attendance in a hospital emergency room. These findings along with the consumption history, the concentrations of drugs and metabolites in urine and serum and the toxicological significance for the interpretation of some MDMA metabolites such as 4-hydroxy-3-methoxymethamphetamine (HMMA) are discussed in this study.     

Bupropion Overdose Resulted in a Pharmacobezoar in a Fatal Bupropion (Wellbutrin®) Sustained‐release Overdose: Postmortem Distribution of Bupropion and its Major Metabolites

Bupropion (BUP) overdose commonly causes generalized seizures and central nervous system depression. The case of a 28‐year‐old woman who died from a massive lethal overdose with sustained‐release bupropion (Wellbutrin^® 300 mg) is herein presented. The autopsy revealed the presence of a pharmacobezoar consisting of at least 40 tablets in the stomach. Determination of bupropion and its active metabolites (hydroxybupropion, threobupropion, erythrobupropion) was achieved by a liquid chromatographic mass spectrometry (LC‐MS/MS) method. Postmortem concentrations for bupropion, hydroxybupropion, threobupropion, and erythrobupropion were obtained in intracranial blood, urine, bile, liver, kidney, and vitreous humor. In this case, intracranial blood level of the parent drug was 1.9 mg/L. Threobupropion was the most abundant metabolite in both blood and urine, 59.3 and 890.6 mg/L. Tissue distribution showed the highest concentration in the liver, 12.3 mg/kg. The 0.8 bupropion concentration ratio vitreous/blood suggested that vitreous could be a valuable specimen for toxicological analysis should postmortem blood be unavailable.     

Urinary excretion profiles of 11-nor-9-carboxy-delta9-tetrahydrocannabinol and 11-hydroxy-delta9-THC: cannabinoid metabolites to creatinine ratio study IV

The objective of this study was to compare urinary excretion patterns of two cannabinoid metabolites in subjects with a history of chronic marijuana use. The first metabolite analyzed was nor-9-carboxy-delta9-tetrahydrocannabinol (delta9-THC-COOH), the major urinary cannabinoid metabolite that is pharmacologically inactive. The second metabolite 11-OH-delta9-THC is an active cannabinoid metabolite and is not routinely measured. Urine specimens were collected from four subjects on 12-20 occasions > or = 96 h apart in an uncontrolled clinical setting. Creatinine was analyzed in each urine specimen by the colorimetric modified Jaffé reaction on a SYVA 30R biochemical analyzer. All urine specimens analyzed for 11-OH-delta9-THC had screened positive for cannabinoids with the EMIT II Plus cannabinoids assay (cut-off 50 ng/mL) on a SYVA 30R analyzer and submitted for delta9-THC-COOH confirmation by GC-MS (cut-off concentration 15 ng/mL). Eleven-OH-delta9-THC was measured by GC-MS with a cut-off concentration of 3 ng/mL. Both GC-MS methods for cannabinoid metabolites used deuterated internal standards for quantitative analysis. The mean (range) of urinary delta9-THC-COOH concentration was 1153 ng/mL (78.7-2634) with a cut-off of 15 ng/mL. The mean (range) of delta9-THC-COOH/creatinine ratios (ng/mL delta9-THC-COOH/mmol/L creatinine) was 84.1 (8.1-122.1). The mean (range) urinary of 11-OH-delta9-THC concentration was 387.6 ng/mL (11.9-783) with a cut-off of 3 ng/mL, and the mean (range) of 11-OH-delta9-THC/creatinine ratio (ng/mL 11-OH-delta9-THC/mmol/L creatinine) was 29.7 (1.2-40.7). Of the 63 urine specimens submitted for delta9-THC-COOH confirmation by GC-MS, 59/63 urine specimens (94%) were positive for delta9 -THC-COOH and 51/63 (81%) were positive for 11-OH-delta9-THC. Overall, the concentrations of 11-OH-delta9-THC in urine specimens collected > or = 96 h apart were lower than delta9-THC-COOH concentrations in 50/51 of the urine specimens in this population. Further urinary cannabinoid excretion studies are needed to assess whether 11-OH-delta9-THC analyses have a role when assessing previous marijuana or hashish use in chronic users whose urine specimens remain positive for delta9-THC-COOH for an extended period of time after last drug use.     

氟硝西泮滥用及检测研究进展

具有镇静催眠作用的氟硝西泮曾在世界范围内被滥用,常被用于自杀、谋杀、迷奸、迷抢等案(事)件。近年其又成为俱乐部滥用药物之一。该药物在体内主要经肝脏代谢为7-氨基氟硝西泮和N-去甲基氟硝西泮,且7-氨基氟硝西泮的血药浓度常常大于血液中的母体药物浓度,大约90%的代谢产物经尿液排出,10%经粪便排出。目前报道的相关分析方法主要是对于血液、尿液、毛发、酒水饮品等检材经LLE、SPE、LPME等净化萃取后,采用毛细管电泳法、色谱法、质谱法及各种技术的联用,检测母体药物及相关代谢产物。本文对氟硝西泮的滥用、体内代谢以及样品的提取净化、仪器分析等进行总结,为相关案(事)件的办理提供参考。     

A 6-year experience with urine drug testing by family service agencies in Nova Scotia, Canada

The objective of this study is to describe a urine drug-testing program implemented for parents with a history of substance abuse by family service agencies in the province of Nova Scotia, Canada. Nurse collectors went to the parents' home to obtain urine specimens under direct observation and then delivered the specimens to the toxicology laboratory or arranged shipment by courier under chain of custody. Each urine specimen was screened for cannabinoids, cocaine metabolite, opiates, amphetamines and benzodiazepines, ethyl alcohol and creatinine. All positive screening tests were confirmed by another method such as gas chromatography-mass spectrometry (GC-MS). In 15,979 urine specimens collected from 1994 to 1999, the percent positive rate for one (or more) drugs/metabolites ranged from 45.6% (1994-1996) to 30.0% (1998, 1999). A total of 575 specimens (3.7%) were dilute (urine creatinine <25mg/dl). Positive rates in 15,404 non-dilute specimens from 1994 to 1999 were as follows: cannabinoids - 11.7%, benzodiazepines - 11.3%, cocaine metabolite - 3.7%, and ethyl alcohol - 2.6%. Most clients provided less than 20 urine specimens for testing but some individuals submitted urine specimens more than 100 times in a 12-15-month period. Urine drug screening in parents with a history of substance abuse provided an objective and reliable indication of recent drug use in this population.     

Identification and quantification of p-hydroxyethylamphetamine as a novel metabolite of ethylamphetamine in rat by gas chromatography-mass spectrometry

Ethylamphetamine and two major metabolites in urine, obtained after intraperitoneal administration of the drug to rats, have been isolated by gas chromatography-mass spectrometry. We have also synthesized an authentic sample of p-hydroxy-N-ethylamphetamine by a simple method. In rat, the metabolic pathway of ethylamphetamine is similar to that of amphetamine and methylamphetamine according to quantitative analysis of the major metabolites using a selected ion monitoring (SIM) method.     

Identification and synthesis of some contaminants present in 4-methoxyamphetamine (PMA) prepared by the Leuckart method

The clandestine synthesis of ring and side chain modified phenylisopropylamines continues to be a major source of these drugs of abuse. One method used for the synthesis of the amphetamine and related compounds involves the treatment of the appropriate ketone with formamide or ammonium formate followed by acid hydrolysis of intermediate N-formyl derivative. In this paper the synthesis of 4-methoxyamphetamine (PMA, 1) by the Leuckart method is investigated. The identification by means of gas chromatography-mass spectrometry (GC-MS) of methoxy derivative of N-(beta-phenylisopropyl)benzaldimine 9, methoxy derivative of N-(beta-phenylisopropyl)benzyl methyl ketimine 5, 1-(4-methoxyphenyl)-N-(4-methoxybenzyl)-2-propanamine 10, (RR/SS) and (RS) 1-(4-methoxyphenyl)-N-[2-(4-methoxyphenyl)-1-methylethyl]-2-propanamine 6a-6c, (RR/SS) and (RS)-1-(4-methoxyphenyl)-N-methyl-N-[2-(4-methoxyphenyl)-1-methylethyl]-2-propanamine 7a-7c, (RR/SS) and (RS)-1-(4-methoxyphenyl)-N-formyl-N-[2-(4-methoxyphenyl)-1-methylethyl]-2-propanamine 8a-8c in crude PMA, are reported. The identity of these compounds was confirmed by independent synthesis of reference compounds. The NMR, MS, IR data, stereochemistry and some chromatographic properties of synthesized compounds are discussed. Finally, the results of the GC-MS analysis of illicitly prepared tablets, containing PMA 1 and 4-methoxymethamphetamine (PMMA, 2), are outlined. The presence of 4-methoxydimethylamphetamine 11, 4-methoxyethylamphetamine 12, and 4-hydroxymethamphetamine 13 are reported in these tablets. The identity of 2, 11, and 12 was confirmed by their independent synthesis.