Musshoff Frank, Lachenmeier Katrin, Lachenmeier Dirk W, Wollersen Heike, Madea Burkhard
Institute of Legal Medicine, University of Bonn, Stiftsplatz 12, D-53111, Bonn, Germany,
Forensic Sci Med Pathol. 2005 Jun;1(2):97-103. doi: 10.1385/FSMP:1:2:097.
After controlled oral administration of D,L-methadone solution (15-260 mg/day) in the context of a methadone-maintenance program, concentrations of methadone and 2-ethylidine-1,5-dimethyl-3,3-diphenyl-l-pyrrolidine (EDDP), in head hair were determined (N=41), using a fully automated headspace solid-phase microextraction procedure in combination with gas chromatography and mass spectrometry (HS-SPME/GC/MS).Methadone was present in all samples in concentrations ranging from 0.25 to 13.29 ng/mg (mean 2.69±0.45 ng/mg). EDDP was also present in every sample in concentrations ranging from 0.05 to 2.17 ng/mg (mean 0.43±0.08). The concentration ratio methadone/EDDP was 7.5±5.7 in the proximal segments, but decreased to 4.8±1.4 in the distal segments. A statistically significant correlation between the intake dose and the methadone and EDDP concentrations in the subjects' hair could be established only in the proximal segments (r=0.913 for methadone and r=0.901 for EDDP), but not in the distal segments. In all, 131 segments analyzed, the correlation coefficient was r=0.760 for methadone and r=0.738 for EDDP. In comparison to the dose-concentration relationship reported in the literature, we found a better correlation with higher correlation coefficients especially in the proximal segments.However, owing to a broad distribution in the correlation between dosage and concentration, the determination of methadone and EDDP in hair holds only limited information about prior methadone administration.
在美沙酮维持治疗项目中,对41名受试者口服D,L-美沙酮溶液(15 - 260毫克/天)进行控制给药后,采用全自动顶空固相微萃取结合气相色谱和质谱法(HS-SPME/GC/MS)测定了头发中美沙酮和2-亚乙基-1,5-二甲基-3,3-二苯基-1-吡咯烷(EDDP)的浓度。所有样本中均检测到美沙酮,浓度范围为0.25至13.29纳克/毫克(平均2.69±0.45纳克/毫克)。每个样本中也都检测到了EDDP,浓度范围为0.05至2.17纳克/毫克(平均0.43±0.08)。近端发段中美沙酮与EDDP的浓度比为7.5±5.7,但在远端发段降至4.8±1.4。仅在近端发段中,受试者头发中美沙酮和EDDP的摄入量与浓度之间能建立统计学上的显著相关性(美沙酮r = 0.913,EDDP r = 0.901),而在远端发段中则未发现显著相关性。在总共分析的131个发段中,美沙酮的相关系数r = 0.760,EDDP的相关系数r = 0.738。与文献报道的剂量-浓度关系相比,我们发现尤其是在近端发段,相关性更好,相关系数更高。然而,由于剂量与浓度之间的相关性分布较广,头发中美沙酮和EDDP的测定对于之前美沙酮给药情况的信息量有限。