The paper reports the establishment of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneous analysis of 11 opiates in hair samples, and the study of presence of opiates in the hair of active heroin addicts. About 20 mg of decontaminated and pulverized hair sample was hydrolyzed with buffer solution for 30 min, in the presence of morphine-d3 and acetylmorphine-d6 used as internal standards, and then extracted with the mixture of dichlormethane and isopropanol, separated by the Allure PFP propyl column with a mobile phase consisting of acetonitrile and 20 mmol L(-1) ammonium acetate buffer, and then analyzed by LC-MS/MS. Multiple reaction monitoring (MRM) mode was used to analyze 11 opiates. Eleven opiates showed a fairly good linearity over the corresponding range (r > 0.996 0). The detection limits were less than 0.05 ng mg(-1). The recoveries were between 47.2% and 110%, and the deviations of intra- and inter-day precision were less than 14%. Heroin, acetylmorphine, morphine, codeine, acetylcodeine and hydrocodone were detected in hair samples of 21 herion addicts. The developed method shows high sensitivity and selectivity, and is suitable for the simultaneous analysis of 11 opiates in hair samples and identify legal and illegal use of opiates.

Objective T o infer the frequency of dosage and m edication history investigate of the victim s in drug facilitated cases by the segm ental analysis of clonazepam in hair. Methods Freezing m illing un-der liquid nitrogen environm ent com bined w ith ultrasonic bath w as used as sam ple pretreatm ent in this study, and liquid chrom atography-tandem m ass spectrom etry w as used for the segm ental analysis of the hair sam ples collected from 6 victim s in different cases. T he concentrations of clonazepam and 7-am in-oclonazepam w ere detected in each hair section. Results C lonazepam and its m etabolite 7-am inoclon-azepam w ere detected in parts of hair sections from the 6 victim s. T he occurrence tim e of drug peak concentration w as consistent w ith the intake tim ing provided by victim s. Conclusion Segm ental analysis of hair can provide the inform ation of frequency of dosage and intake tim ing, w hich show s an unique evidential value in drug facilitated crim es.

Objective T o establish a gas chrom atography-m ass spectrom etry (G C-M S ) m ethod for the determ ination of sulfide ion in blood and apply it to the practical cases. Methods T he 1, 3, 5-tribro-m obenzene w as selected as an internal standard, and 0.2 m L blood sam ple w as collected and analyzed using G C-M S after α-B rom o-2, 3, 4, 5, 6-pentafluorobenzyl brom ide derivatization. Results T he m ass concentration of sulfide ion in blood had good linearity in the range of 0.2-40μg/m L w ith a lim it of detection (L O D ) of 0.05μg/m L . T he m ass concentration of sulfide ion w as less than 0.05μg/m L in blank blood from different sources such as healthy subjects and dead cases. In 3 sulfide poisoning cases, sul-fide ion w as detected in the blood sam ples of 6 victim s, and the m ass concentration range w as 1.02-3.13μg/m L . Conclusion T his study establishes a m ethod for investigation of sulfide ion in blood w hich has been applied successfully to the cases of fatal sulfide poisonings.

Objective T o analyse the m etabolic changes in urine of rats w ith brodifacoum intoxication, and to reveal the m olecular m echanism of brodifacoum-induced toxicity on rats. Methods B y establish-ing a brodifacoum poisoning rats m odel, the urine m etabolic profiling data of rats w ere acquired using high performance liquid chromatography-timeofflightmassspectrometry (HPLC-TOF-M S).The orthogo-nal partial least squares analysis-discrim ination analysis (O PLS-D A ) w as applied for the m ultivariate statistics and the discovery of differential m etabolites closely related to toxicity of brodifacoum . Results O PLS-D A score plot show ed that the urinary m etabolic at different tim e points before and after drug adm inistration had good sim ilarity w ithin tim e period and presented clustering phenom enon. C om paring the urine sam ples of rats before drug adm inistration w ith w hich after drug adm inistration, tw enty-tw o m etabolites related to brodifacoum-induced toxicity w ere selected. Conclusion T he toxic effect of brodi-facoum w orked by disturbing the m etabolic pathw ays in rats such as tricarboxylic cycle, glycolysis, sphin-golipid m etabolism and tryptophan m etabolism , and the toxicity of brodifacoum is characterized of accu-m ulation effect. The m etabonom ic m ethod based on urine H PLC-TO F-M S can provide a novel insight into the study on m olecular m echanism of brodifacoum-induced toxicity.

A sensitive LC-MS/MS method to determine cocaine and its major metabolite benzoylecgonine in guinea pig's hair has been established. About 20 mg of decontaminated hair sample was hydrolyzed with 0.1 mol·L-1 HCl at 50 ℃ overnight, in the presence of cocaine-d3 and benzoylecgonine-d8 used as internal standards, and then extracted with dichlormethane. The analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Positive electrospray ionization (ESI+) and multiple reactions monitoring (MRM) mode were used. The limit of detection (LOD) for cocaine and benzoylecgonine was 1 pg·mg-1. The calibration curves of extracted standards were linear over the range from 5 pg·mg-1 to 250 pg·mg-1 (r2≥0.999 7). The method was validated and applied to the analysis of guinea pig's hair after a single dose administration of cocaine hydrochloride. Cocaine and benzoylecgonine were not only detected, but also quantified in guinea pigs hair.

OBJECTIVE: The possibility for the identification of GHB administration through hair analysis was investigated to provide method and information for toxicology examination of GHB. METHODS A GC/MS assay for GHB in hair was developed. Endogenous levels of GHB in hair, time course of GHB in hair, relationship between GHB levels in hair and hair color or administration dose were also established by guinea pig model. RESULTS: Endogenous levels of GHB in guinea pig black hair and human black hair were (3.01 +/- 1.41) ng/mg (n=28) and (1.02 +/- 0.27) ng/mg (n=20), respectively. GHB levels in black hair were increased by GHB administration and related with drug dosage, and also much higher than in brown and white hair. CONCLUSION Analysis of GHB in hair is suitable for investigation of GHB abuse in forensic toxicology and GHB level in segmental analysis compared with endogenous level of GHB may provide useful information about GHB administration.
Animals ; Dose-Response Relationship, Drug ; Forensic Toxicology/methods* ; Gas Chromatography-Mass Spectrometry/methods* ; Guinea Pigs ; Hair/chemistry* ; Hair Color ; Humans ; Hydroxybutyrates/analysis* ; Male ; Substance Abuse Detection/methods* ; Time Factors

OBJECTIVE: To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detection of mexiletine by liquid chromatography tandem mass spectrometry. METHODS: After simple protein precipitation of the blood sample with acetonitrile, the organic solvent layer diluted with LC mobile solvent was separated by Allure PFP Propyl column, confirmed and quantified by MS/MS in the multi-reaction monitoring (MRM) mode via positive electrospray ionization. RESULTS: Mexiletine and naloxone (internal standard) got ideal resolution under the selected analytical condition. The correlation coeficient of linear calibration curve was over 0.9999 within the mexiletine concentration range 0.02-10 microg/mL. The relative standard deviations were under 10% for intra-day and under 15% for inter-day, and the detection limit was 0.01 microg/mL. CONCLUSION The established LC-MS/MS method is simple, rapid, sensitive, unaffected by matrix effect and appropriate for detection of mexiletine in blood in the field of therapeutic drug monitoring and forensic toxicology.
Anti-Arrhythmia Agents/chemistry* ; Forensic Medicine ; Humans ; Mexiletine/poisoning* ; Molecular Structure ; Naloxone/chemistry* ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrometry, Mass, Electrospray Ionization/methods* ; Tandem Mass Spectrometry/methods*

A sensitive LC-MS/MS method to determine cocaine and its major metabolite benzoylecgonine in guinea pig' s hair has been established. About 20 mg of decontaminated hair sample was hydrolyzed with 0. 1 mol x L(-1) HCl at 50 degrees C overnight, in the presence of cocaine-d3 and benzoylecgonine-d8 used as internal standards, and then extracted with dichlormethane. The analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Positive electrospray ionization (ESI +) and multiple reactions monitoring (MRM) mode were used. The limit of detection (LOD) for cocaine and benzoylecgonine was 1 pg x mg(-1). The calibration curves of extracted standards were linear over the range from 5 pg x mg(-1) to 250 pg x mg(-1) (r2 > or = 0.9997). The method was validated and applied to the analysis of guinea pig's hair after a single dose administration of cocaine hydrochloride. Cocaine and benzoylecgonine were not only detected, but also quantified in guinea pigs hair.
Animals ; Chromatography, High Pressure Liquid ; Cocaine ; administration & dosage ; analogs & derivatives ; analysis ; metabolism ; Guinea Pigs ; Hair ; chemistry ; metabolism ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

Objective To observe the role of Osterix in controlling bone volume in vertebral body and to investigate the possible mechanism .Methods X-ray radiology ,micro CT and HE staining were used to evaluate the change of bone volume in both Osterix knockout and transgenic mice .TRAP staining was used to assess the activity of osteoclasts and immunohistochemistry was used to examine the expression level of RANKL .Results No obvious changes were found in Osterix transgenic mice ,while X-ray examina-tion ,micro CT and HE staining showed that the bone density and bone volume in the lumbar vertebral body increased significantly in OSX null mice 12 weeks after birth .TRAP staining showed that the number of osteoclasts decreased in OSX null mice .IHC re-vealed that the expression level of RANKL was down-regualted in OSX null mice .Conclusion Osterix play an important role in controlling bone volume of vertebral body in mice .

As a keratinized material, nail recently has attracting researchers' attention in the pharmaceuticals analysis. There are comparatively limited studies concerning nail's xenobiotic determination and its mechanism. This article reported the development of a sensitive, specific and reproducible LC-MS/MS method, which could be as a foundation of other studies on drug determination in nail. It can also be regarded as the first report on organic drug in mainland China. Sixteen nail samples from volunteers, who were ingested clozapine for more than nine months, are confirmed positive after being analyzed by the method. It is found that contents of clozapine in the patients' nails are above the nanogram level. Besides, a comparative study of clozapine concentration in nails and hair was made, with a result that there exists a correlation between the two materials in terms of clozapine concentration.
Adult ; Antipsychotic Agents ; pharmacokinetics ; China ; Chromatography, Liquid ; methods ; Clozapine ; pharmacokinetics ; Female ; Hair ; chemistry ; Humans ; Male ; Middle Aged ; Nails ; chemistry ; Psychotic Disorders ; metabolism ; Tandem Mass Spectrometry ; methods