度冷丁滥用者毛发分段分析及其结果评价

以度冷丁滥用者为研究对象,在度冷丁滥用者毛发中检出度冷丁及代谢物去甲度冷丁、N一羟甲基度冷丁和N-乙酰度冷丁。60例度冷丁滥用者头发中度冷丁和去甲度冷丁的含量分别为103±130ng／mg和117±143ng／mg。度冷丁稳定地存在于头发中,检出时限至少为药后20个月,而去甲度冷丁则随着离头发根距离的增加而降低。头发分段分析揭示度冷丁在毛干中的分布和滥用史、剂量和含量存在相关性。     

度冷丁在家兔体内的代谢分布研究

建立生物检材中度冷丁及其代谢物去甲度冷丁的GC／NPD系统分析方法,研究染毒家兔体内度冷丁的原体及代谢物分布情况,测定1例肌肉注射度冷丁过量致死者体内度冷丁和去甲度冷丁浓度。组织检材经酸水解后,在碱性条件下用乙醚提取,残余物用25μl甲醇溶解后进行气相分析。度冷丁的提取回收率高于60％,相对标准偏差小于12％;染毒家兔体内度冷丁浓度下降很快,去甲度冷丁浓度较低;度冷丁和去甲度冷丁在染毒家兔各脏器中含量分布除血液外与度冷丁过量致死者体内分布一致,尿中度冷丁和去甲度冷丁浓度最高,肝脏中浓度明显低于其它脏器。此结果为中毒检案的最佳检材选择和对毒物分析结果评价提供了科学依据。     

尿中度冷丁,去甲度冷丁的浓度分析及评价

本研究考察了5名健康志愿者和140例度冷丁滥用者尿中度冷丁和代谢产物去甲度冷丁的浓度变化，发现二者的代谢物和原体浓度比有显著性差异。提出代谢物和原体的浓度比可以作为判断是否滥用度冷丁的参考依据。     

度冷丁滥用者尿中原体及其代谢产物的分析研究

本研究利用ＧＣ／ＭＳ（ＥＩ．ＰＣＩ）技术，在度冷丁滥用者尿中确认了６种代谢产物。并建立了ＧＣ／ＦＩＤ分析度冷丁及其代谢产物的方法。方法线性范围为０．１～２０μｇ／ｍｌ，变异系数小于１０％，最小检出量为５０ｎｇ／ｍｌ，适用于度冷丁成瘾者尿中含量的测定。     

The stability of tetramine, morphine and meperidine in formalin solution.

The stability of tetramine, morphine and meperidine in formalin solution is an important factor for drug analysis in forensic investigation. In this paper, the tissues (liver, kidney, lung and heart) from poisoned rabbits were immersed in 50 ml 10% formalin solutions for 4 months before examination. We compared the levels of tetramine, morphine, meperidine and the main metabolite normeperidine, measured by GC/NPD or GC-MS, in frozen rabbit tissues, formalin-fixed rabbit tissues, and formalin solution. There was a decrease in the levels of tetramine, morphine, meperidine in formalin-preserved tissues compared with the levels of these drugs in the frozen tissues. It is suggested that the formalin-fixed tissues and formalin solution should be analyzed at the same time to assure the accurate results.     

Tetrahydrocannabinols in hair of hashish smokers

The study investigates the presence of tetrahydrocannabinols in the head hair and the pubic and axillary hair. The hair samples were obtained from hashish smokers. The concentrations were determined by radioimmunoassay and reflect total tetrahydrocannabinols and metabolites. The values found ranged from 0.4 ng/mg hair up to 3.8 ng/mg hair. The presence of the drug in the hair samples was also demonstrated by GC/MS.     

度冷丁在豚鼠毛发中的分布研究

目的探讨度冷丁在毛发中的分布状况。方法通过动物实验-给豚鼠持续腹腔注射度冷丁,探讨度冷丁在豚鼠毛发中出现与消失的时间过程及注射剂量与毛发中的含量关系。结果给豚鼠隔日连续腹腔注射度冷丁7次,第4天可在豚鼠毛发中检出度冷丁,第8天达浓度高峰,停止注射后第5天检不出度冷丁;豚鼠毛发中度冷丁含量与度冷丁的注射剂量有关,但无明显的线性关系。结论研究结果为实际案例分析结果的评价提供依据。     

Detection of antidepressant and antipsychotic drugs in human hair

The presence of therapeutic drugs and their metabolites in the hair of psychiatric patients was investigated using gas chromatography (GC)-mass spectroscopy (MS)-electron ionization (EI) and GC-MS-chemical ionization (CI). In hair samples tested from 35 subjects, carbamazepine, amitriptyline, doxepin, trihexyphenidyl, chlorpromazine, chlorprothixene, trifluoperazine, clozapine and haloperidol were detected, with maximal concentrations of 22.5, 57.7, 183.3, 15.6, 68.2, 30.0, 36.8, 59.2 and 20.1 ng/mg of hair sample, respectively. Chlorpromazine and clozapine concentrations in the hair were found to be dependent on the dosage used and their correlation coefficients were 0.8047 (P<0.001, n=16) and 0.7097 (P<0.001, n=16), respectively. Segmental analysis demonstrated that there was a correlation between the history of subject's drug exposure and the distribution of drug along the hair shaft. Our results also show that drug analysis in hair may provide useful information about drug treatment and the history of usage, and that drugs can be detected in normally kept hair for at least 16 months after intake.     

Simultaneous determination of pethidine (meperidine), phenoperidine, and norpethidine (normeperidine), their common metabolite, by gas chromatography with selective nitrogen detection

This article describes a selective gas chromatographic method for the resolution and quantification of phenoperidine and its two metabolites, pethidine (meperidine) and norpethidine (normeperidine). Drugs and SKF 525 A, the internal standard, are separated from plasma by solvent extraction under alkaline conditions. They are chromatographed on a 3% OV-17 Chromosorb Q glass column and detected with a nitrogen-phosphorous detector. Linearity is observed in the study range (5-200 ng/ml). No interference by endogenous substances is noted.     

Nail analysis for the assessment of caffeine abuse in Northwest China: A population-based study

Caffeine is the most widely consumed psychoactive agent worldwide and has the potential for abuse, but studies monitoring caffeine abuse in China are scarce. This study aims to estimate the prevalence of caffeine abuse in northwest China and investigate the correlation between caffeine and other drugs in hair and nails using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Fingernail clippings were collected from 376 participants in northwest China to detect caffeine and 13 other illicit psychoactive drugs and their metabolites. Paired hair and nail samples were collected from 39 participants to investigate the correlation between caffeine and other drugs in hair and nails. The samples were decontaminated, pulverized, and extracted by a high-throughput nail sample preparation method and analyzed by UPLC-MS/MS. The results showed a risk of caffeine abuse in northwest China, with concentrations ranging from 0.43 to 10.6 ng/mg for healthy volunteers, 0.49–246 ng/mg for caffeine abusers, and 0.25–363 ng/mg for drug addicts in community rehabilitation centers. Caffeine was detected together with other illicit psychoactive drugs and their metabolites. Furthermore, positive detection correlations were found between hair and nail samples. This study provides a current perspective on caffeine abuse in northwest China and demonstrates the practical use of UPLC-MS/MS for the simultaneous detection of caffeine and 13 illicit psychoactive drugs and their metabolites in hair and nails. The results highlight the potential of nails as a supplementary matrix when hair samples are unavailable and emphasize the need for handling caffeine carefully given its potential for abuse.     

The detection of acetylcodeine and 6-acetylmorphine in opiate positive urines

Acetylcodeine (AC), an impurity of illicit heroin synthesis, was investigated as a urinary biomarker for detection of illicit heroin use. One hundred criminal justice urine specimens that had been confirmed positive by GC/MS for morphine at concentrations >5000 ng/ml were analyzed for AC, 6-acetylmorphine (6AM), codeine, norcodeine and morphine. The GC/MS analysis was performed by solid phase extraction and derivatization with propionic anhydride. Total codeine and morphine concentrations were determined by acid hydrolysis and liquid/liquid extraction. AC was detected in 37 samples at concentrations ranging from 2 to 290 ng/ml (median, 11 ng/ml). 6AM was also present in these samples at concentrations ranging from 49 to 12 600 ng/ml (median, 740 ng/ml). Of the 63 specimens negative for AC, 36 were positive for 6AM at concentrations ranging from 12 to 4600 ng/ml (median, 124 ng/ml). When detected, the AC concentrations were an average of 2.2% (0.25 to 10.2%) of the 6AM concentrations. There was a positive relationship between AC concentrations and 6AM concentrations (r=0.878). Due to its very low concentration in urine, AC was found to be a much less reliable biomarker for illicit heroin use than 6AM in workplace or criminal justice urine screening programs. However, AC detection could play an important role in determining if addicts in heroin maintenance programs are supplementing their supervised diacetylmorphine doses with illicit heroin.     

Blood, brain, and hair GHB concentrations following fatal ingestion

Despite the increasing incidence of illicit use of gamma-hydroxybutyrate (GHB), little information is available documenting levels of the drug in GHB fatalities. We measured GHB levels in postmortem blood, brain and hair specimens from a suspected overdose case by gas chromatography/mass spectrometry (GC/MS) following solid phase extraction (SPE) and derivatization with bis(trimethyl-silyl) trifluoroacetamide (BSTFA). Examination found 330 microg/mL GHB in femoral blood and 221 ng/mg GHB in frontal cortex brain tissue, values higher than those typically reported in the literature. The hair shaft was negative for GHB whereas the plucked root bulbs with outer root sheath attached (2,221 ng/mg) and root bulbs after washing and removal of the outer root sheath (47 ng/mg) contained the drug. Our results are consistent with an acute single dose of GHB and, as the toxicology screen was negative for other drugs of abuse, emphasize the significant danger of this drug.     

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.     

Simultaneous Quantitative Determination of Amphetamines,Opiates, Ketamine,Cocaine and Metabolites in Human Hair: Application to Forensic Cases of Drug Abuse

A method using liquid chromatography–tandem mass spectrometry (LC–MS/MS) to simultaneously quantify amphetamines, opiates, ketamine, cocaine, and metabolites in human hair is described. Hair samples (50 mg) were extracted with methanol utilizing cryogenic grinding. Calibration curves for all the analytes were established in the concentration range 0.05–10 ng/mg. The recoveries were above 72%, except for AMP at the limit of quantification (LOQ), which was 48%. The accuracies were within ±20% at the LOQ (0.05 ng/mg) and between −11% and 13.3% at 0.3 and 9.5 ng/mg, respectively. The intraday and interday precisions were within 19.6% and 19.8%, respectively. A proficiency test was applied to the validated method with z-scores within ±2, demonstrating the accuracy of the method for the determination of drugs of abuse in the hair of individuals suspected of abusing drugs. The hair concentration ranges, means, and medians are summarized for abused drugs in 158 authentic cases.     

Testing human hair for cannabis

To validate information on cannabis use, we investigated human hair and pubic hair for cannabinoids (THC and THC-COOH) by gas chromatography/mass spectrometry. Samples (100 mg approximately) were decontaminated with methylene chloride, then pulverized and dissolved in 1 ml 1 N NaOH for 10 min at 95 °C in the presence of 200 ng of deuterated standards. After cooling, samples were extracted by n-hexane/ethyl acetate after acidification with acetic acid. After derivatization of the dry extract by PFPA/PFP-OH, the drugs were separated on a 30-m capillary column and detected using selected-ion monitoring (m/z 377 and 459 for THC and THC-COOH, respectively). Forty-three hair samples were obtained from fatal heroin overdose cases. Among them, 35% tested positive for cannabinoids. Hair concentrations ranged from 0.26 to 2.17 ng/mg (mean, 0.74 ng/mg) and 0.07 to 0.33 ng/mg (mean, 0.16 ng/mg) of THC and THC-COOH, respectively. As is generally the case for other drugs detected in hair, metabolite concentration was always lower when compared to the parent drug concentration. In pubic hair, THC concentrations ranged from 0.34 to 3.91 ng/mg (mean, 1.35 ng/mg) and THC-COOH concentrations from 0.07 to 0.83 ng/mg (mean, 0.28 ng/mg). In most cases, the highest cannabinoid concentration was found in pubic hair, suggesting that this sample may be the more suitable for cannabis testing.     

Determination of amphetamine-type stimulants,ketamine and metabolites in fingernails by gas chromatography–mass spectrometry

A gas chromatography–mass spectrometry (GC–MS) method was developed and validated for the simultaneous qualification and quantification of methamphetamine (MA), amphetamine (AP), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3,4-methylenedioxy-N-amphetamine (MDA), ketamine (KET) and norketamine (NKT) in fingernails. Fingernail samples (20 mg) were washed with distilled water and methanol, digested with 1.0 M sodium hydroxide at 95 °C for 30 min, and then extracted with ethyl acetate. Extract solutions were evaporated to dryness, derivatized using heptafluorobutyric anhydride (HFBA) at 60 °C for 30 min, and analyzed by GC–MS. The linear ranges were 0.1–20.0 ng/mg for AP, MDMA and NKT, 0.2–20.0 ng/mg for MA and MDA, and 0.4–20.0 ng/mg for KET, with the coefficients of determination (r² ≥ 0.9989). The intra- and inter-day precisions were within 7.1% and 10.6%, respectively. The intra- and inter-day accuracies were ?10.9% to 0.8% and ?4.3% to 4.5%, respectively. The limits of detections (LODs) and the limits of quantifications (LOQs) for each analyte were lower than 0.094 ng/mg and 0.314 ng/mg, respectively. The recoveries were in the range of 72.3–94.9%. The average fingernail growth rates of two subjects for three years and six subjects for two months were 3.12 mm/month and 3.16 mm/month, respectively. The method proved to be suitable also for the simultaneous detection and quantification of MA, MDMA, KET and their metabolites in fingernails.     

Simultaneous determination of opiates,cocaine and major metabolites of cocaine in human hair by gas chromotography/mass spectrometry (GC/MS)

A procedure is presented for the simultaneous identification and quantification of morphine (MOR), codeine (COD), ethylmorphine (EM), 6-monoacetylmorphine (6-MAM), cocaine (COC), benzoylecgonine (BZE), ecgonine methylester (EME) and cocaethylene (CE), contained in the hair of opiates and cocaine addicts. The method involves decontamination in dichloromethane, pulverization in a ball mill, heat-acid hydrolysis, addition of deuterated internal standards, liquid-liquid extraction and gas chromatography/mass spectrometry (GC/MS) after silylation. The limit of detection (LOD) was ~0.1–0.8 ng/mg for each drug, using a 30-mg hair sample. The method is reproductible, with a coefficient of variation (CV) of ~8–17%. Cocaine and 6-monoacetylmorphine were the major compounds detected in cases of cocaine (14 cases) and heroin (68 cases) intake. Concentrations were in the range 0.4–78.4 ng/mg (COC), 0.0–36.3 ng/mg (BZE), 0.0–1.6 ng/mg (EME), 0.0–2.1 ng/mg (CE), 0.0–84.3 ng/mg (6-MAM), 0.2–27.1 ng/mg (MOR) and 0.1–19.6 ng/mg (COD). An application in forensic sciences, involving multi-sectional analysis, is given.     

Evaluation of cocaine, amphetamines and cannabis use in university students through hair analysis: preliminary results

The evaluation of drug abuse in a defined population was performed through toxicological hair analysis. Hair samples from university students ranging from 18 to 25 years of age were anonymously collected and screened for cocaine, amphetamines and cannabinoids by radioimmunoassay (RIA). Positive results (cut-off values adopted were 2 ng/mg for cocaine and amphetamines and 0.5 ng/mg for cannabinoids) were confirmed by GC/MS. Preliminary results showed 19% of positive results for cocaine on 200 samples analysed. No confirmed positive results were obtained for amphetamine analysis. RIA technique demonstrated its unsuitability for cannabinoids preliminary screening on hair, giving a high percent of false positive results.     

Benzoylecgonine (cocaine metabolite) detection in hair samples of jail detainees using radioimmunoassay (RIA) and gas chromatography/mass spectrometry (GC/MS)

Benzoylecgonine (BE) was detected in hair samples using nonproprietary extraction methodology and modifications of well-established radioimmunoassay (RIA) screening/quantitative gas chromatography/mass spectrometry (GC/MS) confirmation procedures. Samples collected anonymously from a population of 48 jail detainees weighed between 5.3 and 61.2 mg. All of the 22 hair samples which had RIA results indicating the presence of BE or immunologically similar substances above a cutoff amount of 1.25 ng/sample (50 ng/mL) were confirmed by GC/MS. Several varieties of hair color and texture were tested, although in each general category there were samples which contained BE as well as other samples which did not reveal detectable amounts of BE. The range of concentrations in 22 hair extracts that screened positive were 0.26 to 18 ng/mg hair as determined by GC/MS. In comparison with other reports of cocaine-related substances in hair, these data show consistent concentrations.     

GC/MS、GC/NPD法检测毛发中的氯胺酮

目的采用液-液萃取、衍生化和GC/MS、GC/NPD方法,进行毛发中氯胺酮定性定量分析。方法选择4-苯基丁胺为内标,毛发样本用NaOH、HCl及芳基硫酸酯酶/β-葡萄糖醛酸酶等3种方式进行水解,再进行衍生化后,采用GC/MS和GC/NPD方法定性定量分析。对不同水解和衍生化条件以及提取溶剂进行比较优化,并考察方法精密度、稳定性和检出限。结果方法的提取回收率大于95%,精密度和样品稳定性良好,日内和日间标准偏差小于6%;采用GC/NPD和GC/MS直接分析毛发中的氯胺酮,检出限为0.2ng/mg和2.0ng/mg,线性范围为10.0～250.0ng/mg,相关系数均大于0.99;采用酰化衍生化后分析,GC/NPD和GC/MS检出限分别提高至0.1ng/mg和0.2ng/mg。结论该方法回收率高、检测限低,可以用于毛发中氯胺酮的定性定量分析检验。