Kintz P, Jamey C, Cirimele V, Brenneisen R, Ludes B
Institut de Médecine Légale, Strasbourg, France.
J Anal Toxicol. 1998 Oct;22(6):425-9. doi: 10.1093/jat/22.6.425.
In addition to acetylmorphine (6-AM), acetylcodeine (AC) has been suggested as a marker for the use of illicit heroin. Because no procedure was available for AC testing in hair, a new method was developed for the simultaneous identification and quantitation of morphine (MOR), codeine (COD), 6-AM, and AC. After decontamination, each hair specimen was cut into 1-mm pieces. A 50-mg aliquot was incubated overnight at 50 degrees C in 1 mL Soerensen buffer (pH 7.6) in presence of 200 ng of MOR-d3, COD-d3, 6-AM-d3, and AC-d3. After pH adjustment to 8.4, the analytes were extracted in 5 mL of chloroform/isopropanol/n-heptane (25:10:65, v/v/v). The organic phase was removed and 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. Fifty hair specimens obtained from subjects who died from fatal opiate overdose were analyzed. AC was detected in 22 samples in concentrations ranging from 0.17 to 5.60 ng/mg with a mean value of 1.04 ng/mg. 6-AM was also present in these samples at concentrations ranging from 1.35 to 41.10 ng/mg with a mean value of 7.79 ng/mg. Of the 28 specimens negative for AC, 21 were positive for 6-AM at concentrations ranging from 0.18 to 7.13 ng/mg. When detected, the AC concentrations were an average of 15.5% (2.8 to 32.6%) of the 6-AM concentrations. There was a positive relationship between AC concentrations and 6-AM concentrations (r = 0.915, p = 0.001). Neither AC nor COD was identified in hair specimens collected from 20 subjects taking part in a heroin-maintenance program in Switzerland and receiving pure pharmaceutical heroin hydrochloride daily. Although it is indicative of illicit heroin use, AC would not make a suitable biomarker in place of 6-AM because of its low concentration in hair compared with that of 6-AM and its absence in about 50% of the specimens that tested positive for 6-AM.
除了乙酰吗啡（6-AM）外，乙酰可待因（AC）也被认为是非法使用海洛因的一个标志物。由于当时还没有用于毛发中AC检测的方法，因此开发了一种新方法，用于同时鉴定和定量吗啡（MOR）、可待因（COD）、6-AM和AC。去污后，将每个毛发样本切成1毫米的小段。取50毫克的等分试样，在含有200纳克MOR-d3、COD-d3、6-AM-d3和AC-d3的情况下，于50℃在1毫升索伦森缓冲液（pH 7.6）中孵育过夜。将pH值调至8.4后，用5毫升氯仿/异丙醇/正庚烷（25:10:65，v/v/v）萃取分析物。除去有机相并蒸发至干，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。对50例因阿片类药物过量致死的受试者的毛发样本进行了分析。在22个样本中检测到AC，浓度范围为0.17至5.60纳克/毫克，平均值为1.04纳克/毫克。这些样本中也存在6-AM，浓度范围为1.35至41.10纳克/毫克，平均值为7.79纳克/毫克。在28个AC阴性的样本中，21个6-AM呈阳性，浓度范围为0.18至7.13纳克/毫克。当检测到AC时，其浓度平均为6-AM浓度的15.5%（2.8%至32.6%）。AC浓度与6-AM浓度之间存在正相关（r = 0.915，p = 0.001）。在瑞士参加海洛因维持治疗项目且每天接受纯药用盐酸海洛因的20名受试者采集的毛发样本中，未鉴定出AC和COD。尽管AC表明存在非法使用海洛因的情况，但由于其在毛发中的浓度低于6-AM，且在约50%的6-AM检测呈阳性的样本中不存在，因此AC不适合作为替代6-AM的生物标志物。
