Changes in methamphetamine impurity profiles induced by tert-butoxycarbonylation

Analysis of impurities in methamphetamine (MA) can be used to characterize MA seizures, investigate the relationship among MA seizures, and provide information on their synthetic routes. Recently, chemically derivatized MA, such as tert-butoxycarbonyl (t-Boc) MA, has been seized and attracted attention because routine forensic analysis methods may fail to correctly identify them. Chemical derivatization is a simple method for protection and deprotection of a compound, and protection of MA using t-Boc can be used to mask the MA. Although t-Boc derivatization might alter the impurity profile of MA, the actual changes in the impurity profile have not been investigated. In this study, changes in the MA impurity profile with tert-butoxycarbonylation were explored. MA and some typical impurities were derivatized using di-tert-butyl dicarbonate and water. Analysis of the impurities in five MA samples by gas chromatography showed that peaks both appeared and disappeared for the deprotected MA compared with the original MA. However, typical impurities important for characterizing MA seizures were conserved after derivatization and deprotection. Most of the new peaks were speculated to be contaminants introduced during derivatization and deprotection. A peak giving a mass spectrum similar to that of t-Boc MA was detected in the chromatograms of t-Boc MA and deprotected MA. Although the origin of this peak was not determined, it might be a marker for the MA involving tert-butoxycarbonylation. These results indicate that tert-butoxycarbonylation can alter the MA impurity profile; therefore, care is needed when interpreting results for derivatized MA.     

甲基苯丙胺中毒大鼠纹状体小胶质细胞的激活特性

目的研究甲基苯丙胺（methamphetamine,MA）中毒动物模型纹状体内小胶质细胞（microglia,MG）的激活特性。方法SPF级雄性Wistar大鼠,随机分为对照组和实验组,每组24只。实验组采取腹腔注射MA（15 mg/kg×8次,每次间隔12 h）;对照组按上述给药方式每次注射等量的生理盐水。两组分别于首次注射后第0.5、1、2、3、4、5、6和7天共8个时间点纹状体取材,进行CD-11b抗体免疫组化染色和超微结构观察形态学变化,另对免疫组化染色结果进行细胞激活率计算,并进行统计。结果光、电镜下,各时间点对照组的MG胞体瘦小、突起细长,呈＂细分枝状＂,胞核浓缩,胞质内细胞器稀少;实验组MG胞体变大、突起变短或消失,呈＂灌木丛状＂或＂阿米巴状＂,胞核电子密度降低,胞质内细胞器丰富。对照组各时间点MG的激活率维持在0.15水平以下,且随着观察时间的延长无明显变化趋势;而实验组MG的激活率与对照组相比,第1～7天均显著升高（P〈0.001）。结论MA的刺激可导致MG明显激活。     

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。     

摇头丸中甲基安非他明和咖啡因含量的检验

目的建立了用毛细管电泳分离和测定摇头丸中的甲基安非他明和咖啡因的方法。方法观察缓冲液的种类以及缓冲液的pH值对分离的影响。结果在10～800mg/L的范围内,用Na2HPO4-Na2B4O7和NaH2PO4-Na2HPO4缓冲液,在pH7.0～9.5时,两种药物成分均有较好的线性(r>0.99),三种摇头丸中的甲基安非他明和咖啡因的含量随浓度的增加其回收率增加。结论该分析方法速度快,重现性好,检测结果准确。     

甲基苯丙胺对大鼠认知和脑电图的影响

目的研究甲基苯丙胺（methamphetamine,MA）对脑功能的影响机制,实验设计观察慢性反复使用MA是否同时对大鼠认知行为和脑电活动产生影响。方法 14只雄性SD大鼠（180～200g）随机分为生理盐水注射组（对照组）和MA注射组（实验组5mg/kg体重）每天一次腹腔注射。连续注射7d后进行被动避暗回避行为测试和脑电图检测。结果与对照组相比,实验组大鼠表现为被动避暗回避行为的潜伏期延长,脑电图频谱分析显示δ波相对功率值减小,β波相对功率值增大,差异有统计学意义（P〈0.05）。结论慢性反复使用MA对大鼠被动回避行为和脑电活动均有影响,说明MA滥用造成的认知行为改变与中枢神经系统电生理活性改变有关。     

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.     

甲基苯丙胺在豚鼠毛发中分布及转化的初步研究

目的对甲基苯丙胺在豚鼠毛发中分布及转化机制进行初步研究。方法利用GC/MS,GC/NPD法,测定单次及多次给药豚鼠毛发中MAP、AP的含量变化过程,考察给药剂量与毛发中MAP、AP的含量间的关系,并研究毛发颜色对染毒豚鼠毛发中MAP、AP含量的影响。结果单次及多次给药豚鼠毛发中代谢产物AP均高于原体MAP,给药时间及给药剂量与毛发中MAP、AP的含量显著相关,同体豚鼠黑色毛发中的MAP、AP含量均明显高于棕色、白色毛发。结论给药方式、给药剂量及毛发颜色对豚鼠毛发中MAP、AP的含量均有显著影响。     

Capillary electrophoretic analysis of phosphorus species in clandestine methamphetamine laboratory samples

The clandestine manufacture of methamphetamine is a spreading epidemic. Manufacturing methods are constantly changing, necessitating the implementation of new analytical tools to identify materials from these labs. Characterization of phosphate, phosphite, and hypophosphite ions is necessary to distinguish the various phosphorus-iodine manufacturing methods that are popular methods for reducing pseudoephedrine to methamphetamine. This work describes a capillary electrophoresis method to separate acetate, azide, bromide, carbonate, chlorate, chloride, chromate, fluoride, hypophosphite, iodide, nitrate, nitrite, perchlorate, phosphate, phosphite, sulfate, sulfite, and thiocyanate. The CElixerOA 8.2 dynamic coating system was modified by lowering the capillary temperature to 15 degrees C and using an acid flush between runs to remove adsorbed materials. This allows detection of ions down to between 10 and 30 parts per million with percent relative standard deviations of normalized migration times under 0.1%. This method is a valuable tool for the characterization of phosphate, phosphite, and hypophosphite in routine analysis of clandestine methamphetamine manufacturing evidence and has a broader application in other areas of forensic analysis.     

Detection of methamphetamine in mouse femurs exposed to high temperature

Bone samples are valuable for examining the cause of death and circumstance leading up to death when body fluids are not available for forensic toxicological analysis. Examined were heat-induced changes in methamphetamine and amphetamine concentrations in femurs removed from methamphetamine-injected mice to determine if the burned bones could be used for toxicology testing. The femurs were heated at 100°C, 300°C, or 500°C for 10 or 30 min. The tissue structure of the heated femurs was preserved at 100°C for 30 min but was destructed at higher temperatures. Methamphetamine and amphetamine were detected in femurs heated at 100°C for 10 min, 100°C for 30 min, and 300°C for 10 min (with methamphetamine and amphetamine concentrations ranging from 0.36 to 35 μg/g and 0.54 to 47 μg/g, respectively). Methamphetamine and amphetamine were detectable when heated above their decomposition temperature as a result of limited heat transfer do to protection provide by the femoral muscle. Thus, the bone could be a useful analytical sample in cases of burn-related deaths, where it is difficult to collect body fluids.     

Classical stimulants in Dallas County: A retrospective review of toxicological,seized drug,and demographical data from 2017 to 2022

Cocaine and methamphetamine remain highly abused drugs in the United States due to their euphoric effects. This study examines classical stimulant casework, defined as cases positive for methamphetamine and/or cocaine, received by the Toxicology Laboratory and the Drug Analysis Laboratory at the Dallas County Southwestern Institute of Forensic Sciences from local law enforcement agencies and/or the Office of the Medical Examiner (OME) between January 1, 2017, and December 31, 2022. Methamphetamine positivity increased from 10.4% to 20.3% in the Toxicology Laboratory over the 6 years, whereas cocaine positivity remained relatively stable at approximately 17%. Similarly, in the Drug Analysis Laboratory, the methamphetamine positivity rate changed from 24.8% to 33.2%, whereas cocaine identification remained stable at approximately 20%. Blood concentrations of methamphetamine in OME cases ranged from 10.1–42,740.0 ng/mL while they were lower in DWI casework ranging from 10.2–2385.0 ng/mL. The blood concentration trends of cocaine were similar to methamphetamine, with OME casework ranging higher (10.0–24,501.0 ng/mL) than DWI casework (10.2–371.6 ng/mL). Polydrug use was evident for both methamphetamine and cocaine in postmortem cases, and the top three most frequently co-occurring drug/drug class were opioids/opiates, cannabinoids, and ethanol. The results from this study aid in the understanding of historical usage trends of cocaine and methamphetamine in Dallas County and how those trends have changed over time as newer stimulant drugs have emerged.