Methamphetamine body packer: acute poisoning death due to massive leaking of methamphetamine

We encountered three methamphetamine (MA) body packers presenting simultaneously, one of whom died. Three Nigerian men (39, 35, and 37 years old) who attempted to smuggle were found to contain 35 (498 g), 21 (292 g), and 5 packages (73 g) of methamphetamine hydrochloride (MA-HCl) in their stomachs, respectively. Packages were wrapped with plastic film and Scotch tape. The 39-year-old man died with acute poisoning from c. 20 g of MA-HCl that had leaked from the packages into the stomach. His plasma MA concentration was 8.6 microg/mL when he was hospitalized (17 h before his death). Autopsy findings showed extreme pulmonary congestion and edema as well as moderate hepatic edema and several petechiae. Quantitative analysis was performed by gas chromatography/mass spectrometry. Extremely high concentrations of MA and its metabolite amphetamine (AP) were found in cardiac blood (63.5 microg/mL and 1.2 microg/mL), urine (4,518 microg/mL and 72.4 microg/mL), gastric contents (8,490 microg/mL and 16.9 microg/mL), and in all other autopsy samples. These high concentrations confirmed that the cause of death was acute MA poisoning. Furthermore, impurity-profiling analysis of the seized MA revealed that the MA smuggled by the three suspects originated from the same batch.     

GC法检测血液和尿液中甲基苯丙胺和咖啡因

目的建立同时测定血、尿中甲基苯丙胺和咖啡因含量的方法。方法应用GC／NPD技术,以4-苯基丁胺为内标,直接碱化,用氯仿提取,三氟乙酸酐衍生化,8CB熔融石英毛细管柱（30m×0．25mm×0．25μm）分析。结果生物样品中甲基苯丙胺与咖啡因在0．012—7．5μg/mL浓度范围内线性关系良好,检测限（S／N=3）依次为1．2ng／mL,0．6ng／mL（血）;1．6ng／mL,0．8ng／mL（尿）。苯丙胺在0．017—10．0μg／mL浓度范围内线性关系良好,检测限为1．6mg／mL（血）,3．2ng／mL（尿）。所有样本回收率均大于85％。结论本方法准确、灵敏,适用于血、尿中甲基苯丙胺及其代谢物苯丙胺的三氟乙酸酐衍生化物和咖啡因的同时检测,为判定滥用毒品种类、追查毒品来源以及研究生物体内甲基苯丙胺和咖啡因的交互影响提供了检测手段。     

A case of fatal hemorrhage in the cerebral ventricles following intravenous use of methamphetamine

We describe a case of massive hemorrhage in the cerebral ventricles, probably caused by methamphetamine abuse. A 44-year-old male was found dead in a prone position in a hotel room. Old and new injection marks were observed in his right cubital fossa. Petechiae were observed on the conjunctiva of his right eye, laryngeal mucosa, epicardium and under the capsule of the liver (to a slight or moderate degree). The brain, weighing 1.67 kg, was heavily edematous; the lateral and fourth ventricles were filled with hematomas. Subarachnoid, intracerebral hemorrhages were not observed. Cerebral vascular abnormalities were not evident. There were no remarkable changes in other organs, other than congestion. Gas chromatographic-mass spectrometric analysis of the urine disclosed the presence of methamphetamine and amphetamine. The concentration of methamphetamine within the femoral venous blood and intraventricular hematoma was 0.347 microg/ml and 0.189 microg/g, respectively. Amphetamine was not detected in either sample. Urine contained 3.15 microg/ml methamphetamine and 0.063 microg/ml amphetamine. These results indicate that intraventricular hemorrhage might have occurred shortly after intravenous self-administration of methamphetamine. Cerebral arterial spasm and hypertension resulting from the administration of methamphetamine might have resulted in intraventricular hemorrhage.     

甲基苯丙胺滥用与司来吉兰服用的区分:尿液中甲基苯丙胺和苯丙胺的手性分析

目的考察司来吉兰及其代谢物在尿液中的含量变化,并结合实际案例探讨手性分析区分甲基苯丙胺滥用与司来吉兰服用的可行性。方法采用CHIROBIOTICTM V2手性液相色谱柱对尿液样品进行手性分离和液相色谱-串联质谱(LC-MS/MS)法测定,并对司来吉兰服药志愿者尿样、疑服用司来吉兰的涉毒人员尿样进行甲基苯丙胺和苯丙胺的手性分析。结果服用5 mg司来吉兰后,尿液中司来吉兰的检出时限仅为7h。尿液中R(-)-甲基苯丙胺和R(-)-苯丙胺约在7h质量浓度最高,分别为0.86μg/m L和0.18μg/m L,并在80 h和168 h后无法检出。应用该方法成功分析了疑服用司来吉兰的涉毒人员尿液中甲基苯丙胺和苯丙胺的来源。结论甲基苯丙胺和苯丙胺的手性分析以及司来吉兰代谢物检测可区分甲基苯丙胺滥用与司来吉兰服用。     

Application of solvent microextraction to the analysis of amphetamines and phencyclidine in urine

A fast and simple method to detect some commonly abused illicit drugs, amphetamine, methamphetamine, 3,4-methylendioxy-amphetamine (MDA), 3,4-methylendioxy-methamphetamine (MDMA), 3,4-methylendioxy-N-ethylamphetamine (MDEA) and phencyclidine (PCP) in urine using solvent microextraction (SME) combined with gas chromatography (GC) analysis has been developed. The extraction is conducted by suspending a 2 microl drop of chloroform in a 2 ml urine sample. Following 8 min of extraction, the organic solvent is withdrawn into the syringe and injected into a GC with a pulsed discharge helium ionization detector (PDHID). The effects of different extraction solvents and times, pH and sample preparation were studied. The optimized method was capable of detecting drugs in urine at concentrations below Substance Abuse and Mental Health Services Administration (SAMHSA) established cut-off values for preliminary testing. Good linearity and reproducibility of extraction were obtained. The limits of detection were 0.5 microg/ml for amphetamine, 0.1 microg/ml for methamphetamine and MDA, 0.05 microg/ml for MDMA, 0.025 microg/ml for MDEA and 0.015 microg/ml for PCP. Relative standard deviation (R.S.D.) values ranged between 5 and 20% for the studied drugs.     

CI-mass fragmentographic analysis of methamphetamine and amphetamine in human autopsy tissues after acute methamphetamine poisoning

A 22-year-old male methamphetamine abuser was put under police protection owing to his abnormal state of excitation, but died 1 h later. Distribution of methamphetamine and amphetamine in the body was analyzed by the chemical ionization mass fragmentographic method. Amphetamine/methamphetamine concentrations (μmol/100 g) were $\text{0.24}\text{5.59}$ in blood, $\text{0.41}\text{9.43}$ in liver, $\text{0.41}\text{10.02}$ in brain, $\text{0.37}\text{9.80}$ in kidney, $\text{0.18}\text{4.57}$ in muscle, $\text{0.02}\text{0.63}$ in subcutaneous fat and $\text{1.87}\text{1464}$ in gastric contents. Total amount of methamphetamine hydrochloride in stomach contents was about 54 mg. Amphetamine concentrations in tissues ranged from 3.2% to 4.3% of methamphetamine, and was 0.1% in stomach contents. Amphetamine in tissues seems to be a metabolite of methamphetamine, and amphetamine in gastric contents is presumed to result from gastric mucous excretion. The blood concentration of methamphetamine was at a fatal level, and the total amount of the drug in gastric contents indicates that fatal poisoning occurred by ingestion.     

Achiral and chiral quantification of methamphetamine and amphetamine in human urine by semi-micro column high-performance liquid chromatography and fluorescence detection

In this paper, miniaturized achiral and chiral high-performance liquid chromatographic procedures for the determination of methamphetamine and amphetamine in human urine are described. After a simple pretreatment of human urine (i.e., 10 microL of urine or diluted urine were acidified and dried-up under N2 at room temperature) and fluorescence derivatization with 4-(4,5-diphenyl-1H-imidazol-2-yl)-benzoyl chloride under mild conditions (pH 9.0, 10 min at room temperature), the derivatives were isocratically separated on a semi-micro ODS column with Tris-HCl buffer (0.1 M, pH 7.0): acetonitrile (45 + 55 v/v) at a flow rate of 0.2 mL/min or their enantiomers were separated on a semi-micro OD-RH column with sodium hexafluorophosphate (0.3 M aq.): acetonitrile (44 + 56 v/v) at a flow rate of 0.1 mL/min as the mobile phase. Wide-ranged calibration curves were obtained with detection limits for the achiral and chiral analyses in the atto and femtomol levels, respectively, per injected volume. Satisfactory within- and between-day reproducibility data were obtained with both the methods with the highest relative standard deviation being 9.6%. The methods were applied to the determination of methamphetamine and amphetamine in human urine samples and the concentrations determined by the two methods were well correlated (r = 0.994).     

分子印迹固相萃取法在血中苯丙胺类毒品分析中的应用

目的建立分子印迹固相萃取（MISPE）、GC/MS分析方法,用于血液中苯丙胺类毒品检测。方法 10mmol/L醋酸铵缓冲液（pH8.0）4倍稀释空白添加血液,1mL甲醇,1mL10mmol/L醋酸铵缓冲液（pH8.0）活化苯丙胺类分子印迹固相萃取柱;2×1mL去离子水、1mL60%的乙腈去离子水、1mL1%醋酸乙腈洗涤杂质;2×1mL1%甲酸/甲醇洗脱,洗脱液挥干定容,经GC/NPD、GC/MS分析检测。结果各种苯丙胺类毒品回收率均在90%以上,在20～5 000ng/mL浓度范围内线性关系良好,r2为0.995 7～0.998 9,LOQ在16～30ng/mL之间,LOD在8～15ng/mL之间。结论本方法回收率高,净化效果显著,稳定性好,杂质干扰少,可用于血液中低浓度苯丙胺类毒品的分析检测。     

Prevalence of gamma-hydroxybutyrate (GHB) in serum samples of amphetamine, metamphetamine and ecstasy impaired drivers

Two hundred and forty-seven serum samples which have been collected by police during roadside testing and have been found positive for amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and/or 3,4-methylenedioxyethamphetamine (MDE) were analyzed for gamma-hydroxybutyrate (GHB). Serum samples were spiked with deuterated GHB as internal standard and acetonitrile was added to achieve dilution and protein precipitation. Samples were analyzed with a LC-MS/MS system operated in the multiple reaction monitoring mode (MRM) using a TurboIonSpray source. Chromatographic separation was achieved using a Synergi Polar RP column applying a gradient elution with a runtime of 15 min. To differentiate between endogenous and exogenously administered GHB a cut-off concentration of 10 microg/mL was applied. Five samples exceeded this concentration and were found positive for GHB. These samples were only found positive for amphetamine but no other amphetamine derivatives were detected, while in three samples THC and in one sample cocaine, benzoylecgonine and ethanol were found.     

Rapid and simple method for direct determination of several amphetamines in seized tablets by GC--FID

A simple and rapid method for direct simultaneous determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA) and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in seized tablets was developed using gas chromatography with flame ionization detection. Separation of all six underivatized amphetamines, including diphenylamine as internal standard, was performed in about 6 min, using SPB-50 capillary column. Amphetamine and methamphetamine eluted with negligible tailing while the other amphetamines had highly symmetrical peaks. Sensitivity per component on-column was in the nanogram range, and reproducibility from 2.6 to 6.6% at low concentration (2.4 microg/mL) and from 1.2 to 2.6% at high (70 microg/mL) concentration. The method has a wide linear range, from Limit of detection (LOD) to almost 200 microg/mL, thus allowing analysis of different samples across a wide range of possible concentrations of amphetamines. This simple, fast and precise method using gas chromatography--flame ionization detector (GC--FID), in conjunction with other methods (TLC, IR, HPLC), can be used for identification of amphetamines and direct determination in seized tablets, especially in laboratories with heavy workload.     

Simultaneous analysis of amphetamine, methamphetamine, and 3, 4-methylenedioxymethamphetamine (MDMA) in urine samples by solid-phase extraction, derivatization, and gas chromatography/mass spectrometry

A rapid and effective solid-phase extraction procedure using Bond Elute Certify bonded silica sorbent cartridges was adopted to extract amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) from urine samples. The extract was derivatized with trichloroacetic anhydride prior to gas chromatography/mass spectrometry (GC/MS) analysis with selected ion monitoring of the following ions: 190, 91, 188; 204, 91, 202; 162, 135, 202; 194, 123; and 211, 209 for the derivatized amphetamine, methamphetamine, MDMA, d5-amphetamine, and d9-methamphetamine, respectively. The first of the ions listed for each compound was used for quantitation. The compound d5-amphetamine was used as the internal standard for amphetamine, and d9-methamphetamine was used for methamphetamine and MDMA. Results showed a higher than 65% recovery and a reproducibility with less than a 5% coefficient of variation. When a sample size of 2 mL was used, the lowest detectable concentration was about 50 ng/mL, and a near-perfect fit can be obtained (within the 250 to 4000-ng/mL concentration range studied) using a second-order polynomial model.     

Miniaturized sample preparation method for determination of amphetamines in urine

A simple and miniaturized sample preparation method for determination of amphetamines in urine was developed using on-column derivatization and gas chromatography-mass spectrometry (GC-MS). Urine was directly applied to the extraction column that was pre-packed with Extrelut and sodium carbonate. Amphetamine (AP) and methamphetamine (MA) in urine were adsorbed on the surface of Extrelut. AP and MA were then converted to a free base and derivatized to N-propoxycarbonyl derivatives using propylchloroformate on the column. Pentadeuterated MA was used as an internal standard. The recoveries of AP and MA from urine were 100 and 102%, respectively. The calibration curves showed linearity in the range of 0.50-50 microg/mL for AP and MA in urine. When urine samples containing two different concentrations (0.50 and 5.0 microg/mL) of AP and MA were determined, the intra-day and inter-day coefficients of variation were 1.4-7.7%. This method was applied to 14 medico-legal cases of MA intoxication. The results were compared and a good agreement was obtained with a HPLC method.     

A fatal chronic ketamine poisoning

A few papers in the literature reported incident deaths by acute ketamine poisoning. In this paper, we report an unusual homicide caused by chronic ketamine poisoning. The victim was a 34-year old married woman with no previous medical history (except as reported herein) who died in her own home. The court investigation revealed that she was chronically poisoned by her husband over a period of about one year in an act of homicide. Determination of ketamine concentrations in autopsy specimens was carried out with gas-chromatography/mass spectrometry (GC-MS). The results showed that ketamine concentration was 21 microg/mL in gastric contents, 3.8 microg/mL in blood and 1.2 microg/mL in urine. The most striking forensic findings were cardiac muscle fibrosis and hyaline degeneration of small arteries in victim's heart, the pathological features of ketamine poisoning previous reported only in animal studies.     

A fatal methamphetamine poisoning associated with hyperpyrexia

After self-administration of 0.05g of methamphetamine hydrochloride intravenously on three occasions at intervals of 3h, a 25-year-old female methamphetamine abuser ingested approximately 1.5 g of methamphetamine hydrochloride, and was found dead 3–4 h later. Complete rigor mortis was observed 1–2 h after death and the rectal temperature was 38.4°C 3–4 h after death.Distribution of methamphetamine and amphetamine in the body was analyzed by chemical ionization mass fragmentography. Amphetamine/methamphetamine concentrations (μ mol/100 g) were $\text{0.26}\text{28.8}$ in blood, $\text{0.64}\text{68.2}$ in brain, $\text{0.96}\text{117.1}$ in liver, $\text{0.53}\text{50.6}$ in kidney, and $\text{1.49}\text{1045}$ in stomach contents. Total amount of methamphetamine hydrochloride in stomach contents was 11.6mg.Amphetamine in tissues was a metabolite of methamphetamine, and amphetamine in stomach contents resulted from excretion into saliva and gastric mucous excretion. With rectal temperature at death estimated at more than 41°C, it would seem that hyperpyrexia played an important role in causing death from methamphetamine poisoning.     

超高效液相色谱法（UPLC）同时筛选检测吗啡等7种常见毒品

目的建立快速筛选检测中毒者血液、尿液中吗啡、甲基苯丙胺、苯丙胺、麻黄碱、3，4-亚甲基双氧甲基苯丙胺（MDMA）、3，4-亚甲基双氧苯丙胺（MDA）、氯胺酮并定量分析的方法；方法采用超高效液相色谱（UP—LC）-二极管阵列检测器（PAD）；结果峰面积和质量浓度的线性关系良好，分离效果好、速度快、灵敏度提高；结论该方法与传统的HPLC相比能够更好满足实际办案中吗啡、甲基苯丙胺、苯丙胺、麻黄碱、MDMA、MDA、氯胺酮等中毒者血液、尿液的筛选检测并定量分析。     

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.     

Simultaneous analysis of six amphetamines and analogues in hair, blood and urine by LC-ESI-MS/MS. Application to the determination of MDMA after low ecstasy intake

A rapid and sensitive method using LC-MS/MS triple stage quadrupole for the determination of traces of amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"), 3,4-methylenedioxyethamphetamine (MDEA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in hair, blood and urine has been developed and validated. Chromatography was carried out on an Uptisphere ODB C(18) 5 microm, 2.1 mm x 150 mm column (Interchim, France) with a gradient of acetonitrile and formate 2 mM pH 3.0 buffer. Urine and blood were extracted with Toxitube A (Varian, France). Segmented scalp hair was treated by incubation 15 min at 80 degrees C in NaOH 1M before liquid-liquid extraction with hexane/ethyl acetate (2/1, v/v). The limits of quantification (LOQ) in blood and urine were at 0.1 ng/mL for all analytes. In hair, LOQ was <5 pg/mg for MA, MDMA, MDEA and MBDB, at 14.7 pg/mg for AP and 15.7 pg/mg for MDA. Calibration curves were linear in the range 0.1-50 ng/mL in blood and urine; in the range 5-500 pg/mg for MA, MDMA, MDEA and MBDB, and 20-500 pg/mg for AP and MDA. Inter-day precisions were <13% for all analytes in all matrices. Accuracy was <20% in blood and urine at 1 and 50 ng/mL and <10% in hair at 20 and 250 pg/mg. This method was applied to the determination of MDMA in a forensic case of single administration of ecstasy to a 16-year-old female without her knowledge during a party. She suffered from hyperactivity, sweating and agitation. A first sample of urine was collected a few hours after (T+12h) and tested positive to amphetamines by immunoassay by a clinical laboratory. Blood and urine were sampled for forensic purposes at day 8 (D+8) and scalp hair at day 60 (D+60). No MDMA was detected in blood, but urine and hair were tested positive, respectively at 0.42 ng/mL and at 22 pg/mg in hair only in the segment corresponding to the period of the offence, while no MDA was detectable. This method allows the detection of MDMA up to 8 days in urine after single intake.     

Methamphetamine and amphetamine concentrations in postmortem rabbit tissues

The feasibility of detecting methamphetamine and its major metabolite, amphetamine, in postmortem tissues over a 2-year period was examined. It is important to determine if the abuse and toxic effects of drugs can be proved from evidence found in decayed, submerged, or stained tissue materials. The blood, urine, liver, skeletal muscle, skin and extremity bones from rabbits given methamphetamine intravenously were kept at room temperature, under 4 different conditions: sealed in a test tube, dried in the open air, submerged in tap water and stained on gauze. Methamphetamine was present in all the samples, with slight change in concentration in case of sealed and air dried tissues. Changes varied in bones kept in water. There were considerable decreases in methamphetamine in blood and urine stains. Despite long term storage, drug abuse and/or toxicity could be determined, in all tissues examined.