Synthesis of 2,3- and 3,4-methylenedioxyphenylalkylamines and their regioisomeric differentiation by mass spectral analysis using GC-MS-MS

3,4-methylenedioxyamphetamine (MDA) derivatives are increasingly abused central nervous system stimulants with neurotoxic properties. In recent years a number of controlled substance analogs (designer drugs) with high structural variety reached the illegal market making their identification an arduous task. The underivatized compounds give very similar or even virtually identical electron impact mass spectra containing mainly intense C(n)H(2n+2)N(+) immonium ions. Using tandem mass spectrometry (MS-MS) the additional structural information contained in the collision induced dissoziation (CID) mass spectra of molecular ions using electron impact (EI) and especially chemical ionization (CI) allowed an unequivocal differentiation of 18 studied regioisomeric 1-(methylenedioxyphenyl)-2-propanamines and 1-(methylenedioxyphenyl)-2-butanamines.Further synthetic methods are presented for 1-(3,4-methylenedioxyphenyl)-N-propyl-2-butanamine, N-isopropyl-1-(3,4-methylenedioxyphenyl)-2-butanamine and four 1-(2, 3-methylenedioxyphenyl)-2-butanamines. N-alkylated 1-(3, 4-methylenedioxyphenyl)-2-butanamine compounds (e.g. MBDB) are also known to be abused psychoactive agents (entactogenes) without the sympatomimetic effects of the 3,4-methylenedioxyamphetamines.     

USGS42 and USGS43: human-hair stable hydrogen and oxygen isotopic reference materials and analytical methods for forensic science and implications for published measurement results

Because there are no internationally distributed stable hydrogen and oxygen isotopic reference materials of human hair, the U.S. Geological Survey (USGS) has prepared two such materials, USGS42 and USGS43. These reference materials span values commonly encountered in human hair stable isotope analysis and are isotopically homogeneous at sample sizes larger than 0.2 mg. USGS42 and USGS43 human-hair isotopic reference materials are intended for calibration of δ(2)H and δ(18)O measurements of unknown human hair by quantifying (1) drift with time, (2) mass-dependent isotopic fractionation, and (3) isotope-ratio-scale contraction. While they are intended for measurements of the stable isotopes of hydrogen and oxygen, they also are suitable for measurements of the stable isotopes of carbon, nitrogen, and sulfur in human and mammalian hair. Preliminary isotopic compositions of the non-exchangeable fractions of these materials are USGS42(Tibetan hair)δ(2)H(VSMOW-SLAP) = -78.5 ± 2.3‰ (n = 62) and δ(18)O(VSMOW-SLAP) = +8.56 ± 0.10‰ (n = 18) USGS42(Indian hair)δ(2)H(VSMOW-SLAP) = -50.3 ± 2.8‰ (n = 64) and δ(18)O(VSMOW-SLAP) = +14.11 ± 0.10‰ (n = 18). Using recommended analytical protocols presented herein for δ(2)H(VSMOW-SLAP) and δ(18)O(VSMOW-SLAP) measurements, the least squares fit regression of 11 human hair reference materials is δ(2)H(VSMOW-SLAP) = 6.085δ(2)O(VSMOW-SLAP) - 136.0‰ with an R-square value of 0.95. The δ(2)H difference between the calibrated results of human hair in this investigation and a commonly accepted human-hair relationship is a remarkable 34‰. It is critical that readers pay attention to the δ(2)H(VSMOW-SLAP) and δ(18)O(VSMOW-SLAP) of isotopic reference materials in publications, and they need to adjust the δ(2)H(VSMOW-SLAP) and δ(18)O(VSMOW-SLAP) measurement results of human hair in previous publications, as needed, to ensure all results on are on the same scales.     

(1S,2S)-1-Methylamino-1-phenyl-2-chloropropane: Route specific marker impurity of methamphetamine synthesized from ephedrine via chloroephedrine

Identification of route specific marker impurities of (S)-(+)-methamphetamine can provide us with very useful information for (S)-(+)-methamphetamine abuse criminal investigation. (1S,2S)-(+)-Chloropseudoephedrine and (1R,2S)-(-)-chloroephedrine are well known impurities of (S)-(+)-methamphetamine synthesized by metal catalyzed hydrogenation of (1R,2S)-(-)-ephedrine or (1S,2S)-(+)-pseudoephedrine. In this report (1S,2S)-1-methylamino-1-phenyl-2-chloropropane is identified as a route specific marker impurity from metal catalyzed hydrogenation method for the synthesis of (1R,2S)-(-)-ephedrine or (1S,2S)-(+)-pseudoephedrine via its chloro-derivative. (1S,2S)-1-Methylamino-1-phenyl-2-chloropropane is a ring-opening compound of cis-1,2-dimethyl-3-phenylaziridine by reacting with HCl in high temperature condition of GC inlet.     

Shotgun shooting in northern India--a review (1980-1999)

Central Forensic Science Laboratory (CFSL), Chandigarh undertakes the examination of the crime cases of some northern states of India. The shooting cases of last two decades (1980-1999) involving shotguns were analysed in this laboratory. This paper consists of the study of 360 actual cases of shotguns for evaluation of various parameters, such as type of firearm, number of firearm and firing, location of wound, age, occupation, sex and caste of accused and victim, etc. Out of 360 cases, 253 (70%) were classified as homicidal, 68 (19%) accidental, 11 (3%) suicidal, 9 (2.5%) hunting and 19 (5.5%) cases of insufficient information including the cases of illegal possession of firearm. Single Barrel Breech Loading (SBBL) gun 144 (40%) was preferred over Single Barrel Muzzle Loading (SBML) 109 (30.3%), Double Barrel Breech Loading (DBBL) 72 (20%) and Double Barrel Muzzle Loading (DBML) gun 35 (9.7%). All the breechloader guns were of 12 bore. Muzzleloader gun were recovered only from the remote rural areas. Three hundred and thirty-one (92%) cases involved single, 22 (6%) double and 7 (2%) more than two shotgun. Majority of cases were found of single firing 288 (80%), followed by double 29 (8%) and multi-firing 18 (5%). Eleven (3%) cases were of misfiring and in 14 (4%) cases information was not available. Accidental and suicidal cases had only one firing. The mean age for male and female victim was 31 and 24 years, respectively. Occupationally, agriculture is predominating over business, service and security guards for accused and for victim agriculture followed by service, business, student and security guards are in the descending order. Caste wise the most aggressive community of Kshatriyas is predominating as accused and victim over lower cast people. Head (64%) being a vital part was chosen most frequently for committing suicide followed by body (36%). Service personnel committed maximum number of suicide.     

Hair analysis for delta(9)-THC,delta(9)-THC-COOH,CBN and CBD,by GC/MS-EI. Comparison with GC/MS-NCI for delta(9)-THC-COOH

A sensitive analytical method was developed for quantitative analysis of delta(9)-tetrahydrocannabinol (delta(9)-THC), 11-nor-delta(9)-tetrahydrocannabinol-carboxylic acid (delta(9)-THC-COOH), cannabinol (CBN) and cannabidiol (CBD) in human hair. The identification of delta(9)-THC-COOH in hair would document Cannabis use more effectively than the detection of parent drug (delta(9)-THC) which might have come from environmental exposure. Ketamine was added to hair samples as internal standard for CBN and CBD. Ketoprofen was added to hair samples as internal standard for the other compounds. Samples were hydrolyzed with beta-glucuronidase/arylsulfatase for 2h at 40 degrees C. After cooling, samples were extracted with a liquid-liquid extraction procedure (with chloroform/isopropyl alcohol, after alkalinization, and n-hexane/ethyl acetate, after acidification), which was developed in our laboratory. The extracts were analysed before and after derivatization with pentafluoropropionic anhydride (PFPA) and pentafluoropropanol (PFPOH) using a Hewlett Packard gas chromatographer/mass spectrometer detector, in electron impact mode (GC/MS-EI). Derivatized delta(9)-THC-COOH was also analysed using a Hewlett Packard gas chromatographer/mass spectrometer detector, in negative ion chemical ionization mode (GC/MS-NCI) using methane as the reagent gas. Responses were linear ranging from 0.10 to 5.00 ng/mg hair for delta(9)-THC and CBN, 0.10-10.00 ng/mg hair for CBD, 0.01-5.00 ng/mg for delta(9)-THC-COOH (r(2)>0.99). The intra-assay precisions ranged from <0.01 to 12.40%. Extraction recoveries ranged from 80.9 to 104.0% for delta(9)-THC, 85.9-100.0% for delta(9)-THC-COOH, 76.7-95.8% for CBN and 71.0-94.0% for CBD. The analytical method was applied to 87 human hair samples, obtained from individuals who testified in court of having committed drug related crimes. Quantification of delta(9)-THC-COOH using GC/MS-NCI was found to be more convenient than GC/MS-EI. The latter may give rise to false negatives due to the detection limit.     

Synthesis of standards of the most important markers of Leuckart p-methoxymethamphetamine (PMMA). Examination of the influence of experimental conditions and a drug diluent on SPE/TLC profiling

The synthesis of characteristic markers of PMMA obtained by Leuckart method was described. The effectiveness of a procedure of SPE/TLC screening profiling of impurities was studied on the basis of selected impurities. The influence of glucose (a drug diluent) on the profile quality was investigated. The intermediate product (characteristic for the Leuckart synthesis) N-formyl-p-methoxymethamphetamine (1) and by-products: N-formyl-p-methoxyamphetamine (2), p-methoxyamphetamine (3), N,N-dimethyl-p-methoxyamphetamine (4), (RS) and (RR/SS) diastereoisomers of bis(1-methyl-2-(4-methoxyphenyl)ethyl)amine (meso-5 and rac-5), (RS) and (RR/SS) diastereoisomers of N-methyl-bis(1-methyl-2-(4-methoxyphenyl)ethyl)amine (meso-6 and rac-6), N-methyl-1,3-bis(4-methoxyphenyl)propane-2-amine (7) were synthesized. The substrate p-methoxyphenylacetone and the impurities 1 and 4 were used in the study of influence of experimental conditions and glucose on the profiling process and results. The experiments were carried out according to a 2(4) factorial design. The proposed criterions of the profile quality are based on matrix presentation of TLC patterns. They take into account the number of spots revealed, differences between R(f) values and intensity of fluorescence, simultaneously.     

The association between body mass index and pulmonary thromboembolism in an autopsy population

Abstract: To evaluate the association between obesity and pulmonary thromboembolism (PTE) in a forensic context, 160 autopsy cases of fatal PTE were compared with age‐ and gender‐matched controls. The mean age of cases was 66 years (range 26–98 years; M/F 74:86). The mean body mass index (BMI) of cases with PTE was 30.88 (range 14.95–79.51), which was significantly higher than in the controls (mean BMI = 25.33; range 12.49–61.84) (p < 0.0001). Comparing the group with PTE with controls showed that five (3.1%) compared to 20 (12.5%) were underweight, 39 (24.4%) compared to 67 (41.88%) were of normal weight, 49 (30.63%) compared to 43 (26.88%) were overweight, 43 (26.88%) compared to 24 (15%) were obese, and 24 (15.0%) compared to six (3.75%) were morbidly obese. In each category of above‐normal BMIs, there were significantly greater numbers in the groups with PTE: overweight (p < 0.01), obese (p < 0.001), and morbidly obese (p < 0.0001).     

中日法律的近代转型的比较分析

19世纪中叶 ,中日两国均在西方殖民主义的武力威胁之下 ,开始了法律的近代化转型 ,但又有所差别 ,表现在 :一、社会背景不同。二、变革过程不同。三、主体不同。四、立法目的不同。五、具体内容与实施程度不同。六、历史作用不同。     

Simultaneous phenotyping of genetic markers for paternity testing

Time-and cost-saving methods for paternity testing are described. Seventeen genetic systems were divided into six groups: (1) transferrin (Tf), factor B (Bf), and phosphoglucomutase 1 (PGM1); (2) group-specific component (Gc) or alpha 1-antitrypsin (PI) and alpha 2HS-glycoprotein (HSGA); (3) complement components C6 and C7, factor 13B (F13B), and plasminogen (PLG); (4) haptoglobin (Hp), C8 alpha-gamma chain (C81), and factor I (IF); (5) red cell acid phosphatase (ACP), esterase D (ESD), and glutamic-pyruvic transaminase (GPT); and (6) 6-phosphogluconate dehydrogenase (PGD) and glyoxalase I (GLO). Each group of systems was typed simultaneously by electrophoresis or isoelectric focusing (IEF) followed by staining or immunoblotting. These methods are very practical because they afford a considerable saving of time, work and expense, and facilitate semipermanent preservation of electrophoretic patterns.     

Ten methods for calculating the uncertainty of measurement

While forensic laboratories are coming under increasing pressure to provide meaningful estimates of measurement uncertainty, there has been little discussion of this topic in the literature. This article summarizes ten bases for estimating this parameter: (1) proficiency tests; (2) readability limits; (3) independent reference materials; (4) operational limits applied during calibration; (5) expert judgment; (6) precision control samples without (6) and with (7) contributions from extramural sources of error; (8) error budgets; (9) historical performance; and (10) ruggedness tests. Based on the assumptions underlying each approach, the forensic community will need to apply a variety of discipline-specific approaches to arrive at satisfactory estimates of measurement uncertainty.     

Exemption of certain systems of records under the Privacy Act. Final rule

This final rule exempts four systems of records (SORs) from subsections (c)(3), (d)(1) through (d)(4), (e)(4)(G) and (H), and (f) of the Privacy Act pursuant to 5 U.S.C. 552a(k)(2): The Automated Survey Processing Environment (ASPEN) Complaint/ Incidents Tracking System (ACTS), HHS/CMS, System No. 09-70-0565; the Health Insurance Portability and Accountability Act (HIPAA) Information Tracking System (HITS), HHS/CMS, System No. 09-70-0544; the Organ Procurement Organizations System (OPOS), HHS/CMS, System No. 09-70- 0575; and the Fraud Investigation Database (FID), HHS/CMS, System No. 09-70-0527.     

Identification and synthesis of by-products found in 4-methylthioamphetamine (4-MTA) produced by the Leuckart method

The synthesis of the designer drug 4-methylthioamphetamine (4-MTA) has been carried out using the well-known Leuckart reaction in four versions. The treatment of 4-methylthiophenylacetone with formamide, mixture of formamide/formic acid, ammonium formate, and mixture of ammonium formate and formic acid followed by acid hydrolysis brought about the formation of 4-MTA contaminated with a number of impurities. The gas chromatography mass-spectrometry (GC-MS) analysis of the reaction mixtures allowed identification of the most prominent impurities, such as diasteromers of N,N-di-[β-(4-methylthiophenyl)isopropyl]amine, N,N-di-[β-(4-methylthiophenyl)isopropyl]methylamine, N,N-di-[β-(4-methylthiophenyl)isopropyl]formamide, the Schiff bases derived from 4-MTA and 4-methylbenzaldehyde (benzaldimine) and 4-methylthiophenylacetone (ketimine) as well as some heterocycles: 4-methyl-5-(4'-methylthiophenyl)pyrimidine, 4-(4'-methylthiobenzyl)pyrimidine, 2,6-dimethyl-3,5-di-(4'-methylthiophenyl)pyridine, 2,4-dimethyl-3,5-di-(4'-methylthiophenyl)pyridine. The correctness of identification was confirmed by independent synthesis of these compounds. Each synthesized reference compound was characterized by means of MS, (1)H and (13)C NMR, and IR methods. The stereochemistry of (RR/SS) diasteromer of N,N-di-[β-(4-methylthiophenyl)isopropyl]amine was confirmed by a crystallographic method.     

Gm(11) grouping of dried bloodstains

An absorption inhibition method for the detection of gamma marker Gm(11) in dried bloodstains is described. Particular reference is made to the association of Gm(11) with Gm(-1, -2). When a dried bloodstain fails to inhibit anti-Gm(1) and anti-Gm(2), this may represent a true Gm(-1, -2) result or there may be insufficient material to inhibit either antibody. The detection of Gm(11) in a bloodstain extract provides an objective means of confirming the apparent absence of Gm(1) and Gm(2) as representing a true Gm(-1, -2) result. This antigen compares very well with other blood group systems with regard to the amount of bloodstain required for analysis and its stability. No evidence is available for preferential loss of Gm(1) and Gm(2) relative to Gm(11) in dried bloodstains.     

Disentangling the Disability Quagmire in Psychological Injury and Law

This paper aims to critically analyze the evolution of six models of conceptualization, determination, and prediction of occupational disability relevant in the medico-legal context of psychological injury. The six models are the (a) biomedical, (b) forensic, (c) psychosocial, (d) ecological, (e) economic, and (f) biopsychosocial. We will discuss the key commonalities and differences among the models, including disciplinary tradition, research paradigm, recognition of person–environment interaction, key tenets, and implications for practice and research in psychological injury. The paper will highlight and discuss psychosocial issues, often underemphasized in forensic psychological practice, including: (a) balanced assessment of primary, secondary, and tertiary gains and losses, (b) self-perception, (c) disability identity, (d) beliefs and expectations, (e) coping, (f) adaptation and positive growth, (g) social stigma and social reactions to disability, including disability harassment, and (h) recognition of system-based environmental influences and demands. We will provide a special focus on the current state of the science and practice of prediction of disability, of particular interest to researchers and clinicians involved in clinical and occupational prognostication in psychological injuries. Finally, we will draw conclusions and recommendations for future research and best practices in the psychological injury area using a cross-diagnostic, dynamic, functionally based, and integrated biopsychosocial and forensic model of disability.     

A fatality caused by accidental production of hydrogen sulfide.

A 55-year-old male Caucasian truck driver was dead at the scene after breathing hydrogen sulfide (H(2)S) produced by an accidental transfer of sodium hydrogen sulfide (NaHS) from a tanker truck to a tank containing 4% sulfuric acid (H(2)SO(4)) and iron(II) sulfate (FeSO(4)). Autopsy of the decedent's body revealed pulmonary edema and passive congestion in lungs, spleen, kidneys, and adrenal glands. Postmortem biological samples were analyzed for carbon monoxide, cyanide, ethanol, and drugs. Since a potential exposure to H(2)S was involved, blood was also analyzed for sulfide (S(2-)). The analysis entailed isolating S(2-) from blood as H(2)S using 0.5M H(3)PO(4), trapping the gas in 0.1M NaOH, and determining the electromotive force using a sulfide ion specific electrode. Acetaminophen at a concentration of 14.3 microg/ml was found in blood, and metoprolol was detected in the blood, liver, and kidney samples. The blood S(2-) level was determined to be 1.68 microg/ml. It is concluded that the cause of death was H(2)S poisoning associated with a hazardous material accident in an industrial situation.     

水和生物体液中3种镇痛麻醉药中空纤维膜液相微萃取

目的研究采用中空纤维膜液相微萃取(hollowfiber liquid phase microextraction,HF-LPME)法提取水和生物体液中的哌替啶,氯胺酮,曲马多。方法样品调节至pH11.5和盐饱和,磁力搅拌器转速为600转/min,内标为盐酸萘福泮,取4μl甲苯,注入到聚偏氟乙烯中空纤维膜中,萃取20min,抽回1μl甲苯进入GC中进行分析。结果血浆、尿、水相关系数R2:哌替啶分别为0.9935、0.9981、0.9997,氯胺酮分别为0.9906、0.9913、0.9927,曲马多分别为0.9741、0.9913、0.9970;检测限:水、尿中哌替啶、氯胺酮、曲马多均为0.01μg/ml,血浆中哌替啶、氯胺酮、曲马多均为0.05μg/ml;血浆、尿、水日内RSD:哌替啶分别为13.0%、7.3%、4.6%,氯胺酮分别为15.1%、13.6%、1.4%,曲马多分别为3.7%、4.3%、9.0%;血浆、尿、水日间RSD:哌替啶分别为15.1%、13.5%、12.2%,氯胺酮分别为12.3%、5.3%、6.0%,曲马多分别为7.1%、15.5%、11.9%;血浆、尿、水相对回收率:哌替啶分别为109.80%、93.49%、97.57%,氯胺酮分别为91.09%、101.80%、100.40%,曲马多分别为106.40%、92.94%、113.32%。结论中空纤维膜液相微萃取用于水和生物体液中的哌替啶,氯胺酮,曲马多的分析,所需有机溶剂少,避免残留和交叉污染,集萃取,富集,进样于一步完成,简单,高效,实用。     

“法”义新论

"法"在字源和词源上有三个系统,即灋、佱、。许慎在《说文》中仅以战国篆文为据,未能考察商至战国前期文字发展的理路,对"灋"的词源解释有误。廌与作为神兽的獬豸有差异,并无掌法神兽之义。灋字在西周时代作为"废"的本字使用,与后世的"法"义并无关联。宗周文化系统中有一个表规范、法则意义的"佱"字;南方文化中有一个表达规范、法则、效法甚至法律的"",因此在先秦时代有宗周的"佱"和南方的""两个与后世"法"有渊源关系的概念系统。这两个系统在春秋中叶至战国时代发生碰撞、融合,最终以""吸纳并取代"佱",并写作"灋"为终结。具有"刑罚"、"审判"之义的"法",通过"灋"的字源和词源无法解释,而当与宗周文化系统之外的南方文化中的系统有关。     

Ethical questions raised by human genetics. A personal contribution to the preparation of a legal instrument of the Council of Europe on human genetics (part I).

(1) Classification of so-called "genetic" diseases. (1.1) Diseases linked to chromosomal abnormalities. (1.2) Monogenic diseases. (1.3) Polygenic and multifactorial diseases. (1.4) Mitochondrial diseases. (1.5) Diseases involving infectious agents. (2) Genetic screening and diagnoses. (2.1) Community screening and genetics. (2.2) Prenuptial genetic diagnosis. (2.3) Pre-ICSI diagnosis. (2.4) Pre-implantation diagnosis. (2.5) Prenatal diagnosis. (2.6) Neonatal diagnosis. (3) Access to screening and diagnosis results.     

听力正常人听性稳态反应阈值与纯音测听阈值的比较

目的 通过比较听性稳态反应（auditory steady-state responses,ASSR）阈值与纯音测听（pure tone audiometry,PTA）阈值,为ASSR技术应用于听力障碍法医学鉴定提供技术数据。建立本实验室ASSR阈值与PTA阈值的校正值。方法 对27例（54耳）正常听力志愿者进行PTA及500、1000、2000和4000Hz的ASSR测试,采用配对t检验法比较测试耳ASSR闽值与PTA阈值的关系;并验证Smart EP-ASSR测试系统校正后的ASSR阈值与PTA阈值的一致性。结果 正常耳ASSR阈值较PTA阈值高（P〈0．05）,各频率差值：500Hz为（22．04±5．79）dB,1000Hz为（11．02±5．44）dB,2000Hz为（12．59±5．89）dB,4000Hz为（17．78±7．25）dB;仪器校正后的ASSR阈值与PTA阈值的差值：500Hz为（-3．96±5．79）dB,1000Hz为（0．02±5．44）dB,2000Hz为（-0．41±5．89）dB,4000Hz为（-1．25±7．25）dB。结论 听力正常人ASSR阈值较盯A阈值高,其差值在各频率不一致．平均为16．9dB。ASSR用于听力障碍法医学鉴定中评估行为听阈时,ASSR阈值需要进行校正。     

Results of the GEP-ISFG collaborative study on two Y-STRs tetraplexes: GEPY I (DYS461, GATA C4, DYS437 and DYS438) and GEPY II (DYS460, GATA A10, GATA H4 and DYS439)

A collaborative exercise was carried out by the Spanish and Portuguese ISFG Working Group (GEP-ISFG) in order to evaluate the performance of two Y-chromosome STR PCR tetraplexes, which include the loci DYS461, GATA C4, DYS437 and DYS438 (GEPY I), and DYS460, GATA A10, GATA H4 and DYS439 (GEPY II). The participating laboratories were asked to type three samples for the eight markers, using a specific amplification protocol. In addition, two control samples, with known haplotypes, were provided. The results obtained by the 13 different participating laboratories were identical, except for two laboratories that failed to type correctly the same two samples for GATA C4. By sequence analyses, two different GATA C4 allele structures were found. One control sample (allele 21) and two questioned samples (allele 22, correctly typed by all the laboratories, and allele 25) presented the following repeat structure: (TCTA)4(TGTA)2(TCTA)2(TGTA)2(TCTA)n, but different from the one found for allele 26 in one sample included in this exercise, as well as in the second control sample (allele 23), namely (TCTA)4(TGTA)2(TCTA)2(TGTA)2(TCTA)2(TGTA)2(TCTA)n. The collaborative exercise results proved that both Y-tetraplexes produce good amplification results, with the advantage of being efficiently typed using different separation and detection methodologies. However, since GATA C4 repeat presents a complex structure, with alleles differing in sequence structure, efficient denaturing conditions should be followed in order to avoid typing errors due to sizing problems.