Kintz P, Bundeli P, Brenneisen R, Ludes B
Institut de Médecine Légale, Strasbourg, France.
J Anal Toxicol. 1998 May-Jun;22(3):231-6. doi: 10.1093/jat/22.3.231.
Hair specimens were collected from the vertex area of 20 subjects taking part in a heroin-maintenance program. Subjects were administered, under controlled conditions, heroin hydrochloride in 2 or 3 doses/day intravenously. Heroin doses ranged from 30 to 800 mg/day, and were self-administered. In all cases, a 4-cm segment from the proximal zone (root) was analyzed, which corresponded to about 100 days of hair growth. During that period, total heroin administered ranged from 14,100 to 71,540 mg. All special features of hair such as coloring, bleaching, etc. were noted. Each sample was washed twice with dichloromethane (5 mL, 2 min) and, after drying, cut into small pieces of approximately 1 mm. A 30-35-mg aliquot was incubated overnight at 45 degrees C in 1 mL methanol in the presence of 200 ng of heroin-d9, 6-acetylmorphine-d3, and morphine-d3. The methanolic extract was then evaporated to dryness, and the residue was derivatized by silylation (BSTFA + 1% TMCS). Drugs were analyzed by gas chromatography-mass spectrometry in electron impact mode. Limits of quantitation were set to 0.1 ng/mg. Concentrations ranged from 0 to 4.53, 0.38 to 10.11, and 0.71 to 5.20 ng/mg for heroin, 6-acetylmorphine, and morphine, respectively. 6-Acetylmorphine was the major analyte present in hair in all but five cases. Heroin was present in the highest concentration in three cases, and morphine was the major metabolite in two cases, probably because of hydrolysis. Subjects tested positive for heroin in all but two cases. No correlation between the doses of administered heroin and the concentrations of total opiates in hair was observed (r = 0.346). However, when considering a single analyte, it was observed that the correlation coefficient seemed to be linked to its plasma half-life. A weak correlation coefficient corresponds to a drug with a short plasma half-life, and the correlation coefficient increases when plasma half-life increases, as r = 0.12, 0.25, and 0.64 for heroin, 6-acetylmorphine, and morphine, respectively. These results suggest that using quantitative drug measurements in hair to determine the amount of drug ingested will remain inapplicable until more is known about the factors that may influence the incorporation of drugs into hair and a way to reduce the observed variability.
从参与海洛因维持治疗项目的20名受试者的头顶区域采集毛发样本。在受控条件下，受试者静脉注射盐酸海洛因，每日2或3次。海洛因剂量范围为30至800毫克/天，由受试者自行给药。在所有情况下，分析近端区域（根部）4厘米长的一段毛发，这大约相当于100天的头发生长。在此期间，海洛因给药总量为14100至71540毫克。记录毛发的所有特殊特征，如染色、漂白等。每个样本用二氯甲烷（5毫升，2分钟）洗涤两次，干燥后切成约1毫米的小块。取30 - 35毫克的等分试样，在45℃下于1毫升甲醇中与200纳克海洛因 - d9、6 - 乙酰吗啡 - d3和吗啡 - d3一起孵育过夜。然后将甲醇提取物蒸发至干，残留物通过硅烷化（BSTFA + 1% TMCS）进行衍生化。通过电子轰击模式的气相色谱 - 质谱联用仪分析药物。定量限设定为0.1纳克/毫克。海洛因、6 - 乙酰吗啡和吗啡的浓度分别为0至4.53、0.38至10.11和0.71至5.20纳克/毫克。除5例之外，6 - 乙酰吗啡是毛发中存在的主要分析物。在3例中，海洛因浓度最高，在2例中，吗啡是主要代谢物，可能是由于水解作用。除2例之外，所有受试者的海洛因检测均呈阳性。未观察到给药海洛因剂量与毛发中总阿片类药物浓度之间的相关性（r = 0.346）。然而，当考虑单一分析物时，观察到相关系数似乎与其血浆半衰期有关。弱相关系数对应于血浆半衰期短的药物，随着血浆半衰期增加，相关系数增大，海洛因、6 - 乙酰吗啡和吗啡的相关系数分别为r = 0.12、0.25和0.64。这些结果表明，在更多地了解可能影响药物掺入毛发的因素以及减少观察到的变异性的方法之前，利用毛发中的药物定量测量来确定摄入的药物量仍然不可行。
