Pharmacokinetics Of Disappearance Of Heroin And Its Metabolites From Hair After Discontinuation

Heroin addiction is one of the most serious social problems in China, for heroinaddicts, stop abuse is the biggest concern of the whole society. Hair could be acomplement to the fluid material, gives particular advantages such as the stability of aspecimen, non-invasion sampling, broad time detection window. Now hair analysis had awidespread application in the field of forensic science and clinical toxicological analysis.But, because the mechanism and process of drug elimination in hair was not fullyunderstood, the result of expert conclusion in the case of heroin addiction had manyproblem to be solved.Segmental hair analysis not only could provide useful information over a wideperiod of time, but also can be affected by the speed of hair growth, the growth cycle, themetabolism of drug incorporate into hair, hair sampling. The speed of hair growth isroughly0.7-1.4cm/month, as each hair didn’t in the same stage of hair growth cycle, thesection of the shaft that trapped the drug will continue to move away from the scalp inthe hairs in anagen phase, but will remain motionless in the hairs in telogen phase, a drugwill unlikely be found in the same place in each hair. Drug-free hair would becontaminated with drug-containing hair in the telogen phase that has stopped growingthat can make positive result, moreover the deviation in the process of hair sampling andsegmental analysis also could make positive result. Based on the above reasons, ourresearch hypothesed that heroin and its metabolites could be detected in the hair segmentof proximal to the scalp after abstinence. In present, the study of evaluate thepharmacokinetics of disappearance of heroin and its metabolites, acetylmorphine andmorphine, from hair after discontinuation of heroin use has not been reported. Based on the above assumptions, we established a liquid chromatography-tandemmass spectrometry for simultaneous analysis of11opiates in hair samples, and studiedthe presence of opiates in the hair of actived heroin addicts, and evaluated thepharmacokinetics of disappearance of heroin and its metabolites, confirmed theelimination half-life in hair. The results will provide basic data of hair analysis and resultinterpretation, and will have important application value in the judicial practice.The major results and conclusions are listed as follows:1. Established a liquid chromatography-tandem mass spectrometry (LC-MS/MS) forsimultaneous analysis of11opiates in hair samplesThe method analysed11opiates in hair, including morphine, heroin, acetylmorphine,codeine, hydrocodone, thebaine, papaverine, acetylcodeine, dihydrocodeine,normorphine, norcodeine. The detection limits were less than0.05ng·mg1. Therecoveries were between47.2%and110%. The developed method showed highsensitivity and selectivity, and was suitable for the simultaneous analysis of11opiates inhair samples and expanding the range of targets.2. Disposition of opiates in positive hairs of heroin abusers during2010—2011inour lab were investigated. There were heroin, acetylmorphine, morphine, codeine,acetylcodeine, hydrocodone, papaverine, and so on. The concentrations ofacetylmorphine and morphine were in the range of0.2ng mg-1—26.05ng mg-1and0.11ng mg-1—7.13ng mg-1, respectively. The ratios of acetylmorphine and morphine werebetween0.81and36.13, which conform to the criteria of heroin positive in hair publishedby SOHT.3. The pharmacokinetics of disappearance of heroin and its metabolites wereconducted by segmental hair analysis of32hairs of heroin addicts after rehabilitation of4-5months. The results of elimination half-life of acetylmorphine, morphine and codeinein hair were(0.88±0.40)、(0.73±0.23) and (0.61±0.21) months, elimination rate constantwere(0.95±0.41) ng·mg-1·cm-1、(1.06±0.36) ng·mg-1·cm-1and (1.26±0.43)ng·mg-1·cm-1respectively, implied that approximately3—4months had to pass for hair testing to become negative in the segment proximal to the scalp. The result wouldpropose the time of hair sampling for heroin addicts after rehabilitation. Overall, theinnovation points and the significance of our study summarized as follows:1. Developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)with high sensitivity and wide range for simultaneous analysis of11opiates in hairsamples.2. Studied on existing conditions and distribution of11alkaloid opiates in hair fromheroin addicts comprehensively. The characteristics and confirm criterion of heroinpositive hair were discussed. These data are suitable reference values are the basis for theinterpretation of results from investigations into the abuse of heroin.3. For the first time, the pharmacokinetics of disappearance of heroin and itsmetabolites in hair of heroin abstinence were investigated, and first reported eliminationhalf-life of acetylmorphine, morphine and codeine in hair. This finding should beincorporated in interpreting compliance with abstinence of former drug users.