Smith M L, Shimomura E T, Summers J, Paul B D, Jenkins A J, Darwin W D, Cone E J
Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
J Anal Toxicol. 2001 Oct;25(7):504-14. doi: 10.1093/jat/25.7.504.
Heroin is one of the major target drugs in workplace drug-testing programs because of its history of abuse, liability, and continued negative social impact. This study was a comprehensive examination of pharmacokinetics, pharmacodynamics, detection times, opiate immunoassay performance, and urine excretion profiles following single doses of heroin administered to human subjects via smoking and intravenous routes. Studies of the first four components of this investigation were previously published. This article describes the urine excretion profiles. Total morphine (Tmor), free morphine (Fmor), and 6-acetylmorphine (6-AM) were measured by gas chromatography-mass spectrometry (GC-MS) in 920 urine samples collected from 11 male human subjects following single doses of heroin. Eight received intravenous doses of 3, 6, and 12 mg heroin HCI and four smoked 3.5-, 5.2-, 7-, 10.5-, or 13.9-mg doses of heroin (base). In addition, 183 urine-based blind quality-control samples were added to the study set to assess assay performance. Creatinine was also measured in each sample by a colorimetric technique. The parameters studied were not significantly dependent on route of administration. Excretion half-life mean +/- SD for Tmor was 3.11 +/- 0.30 h. Range (median) of peak urine concentrations, time to peak, time to last positive sample for low cutoff (300 ng/mL) and high cutoff (2000 ng/mL) for Tmor following lower doses (< or = 7 mg) were, respectively, 1392-9250 (3620) ng/mL, 1.2-6.2 (2.3) h, 7.4-31.9 (7.4) h, and 0-10.1 (4.3) h. Following higher doses (> 10 mg) they were 2065-29,030 (16,470) ng/mL, 2.3-9.3 (4.5) h, 10.7-53.5 (34.4) h, 2.3-22.3 (8.3) h. Fmor peaked in the same sample as Tmor. Range (median) of peak Fmor concentrations and time to last positive using a cutoff of 100 ng/mL for low and high doses were, respectively, 117-1160 (415) ng/mL, 1.2-10.1 (4.5) h and 150-2580 (1400) ng/mL, 2.3-29.1 (9.3) h. The range (median) of peak urine concentrations for 6-AM was 6.1-568 (124) ng/mL. In general, the first urine void had the peak 6-AM concentration and was the only specimen positive at a 10-ng/mL cutoff. As previously reported urine concentrations varied greatly between subjects and within subjects with time after dosing but were much more predictable when values were reported as amount of drug per unit of creatinine. The range (median) values for percent of heroin excreted into urine as Tmor was 12.8-88.5% (51.0).
由于海洛因的滥用历史、危害性及持续的负面社会影响，它是工作场所药物检测项目中的主要目标药物之一。本研究全面考察了通过吸烟和静脉注射途径向人体受试者单次给药海洛因后的药代动力学、药效学、检测时间、阿片类免疫分析性能及尿液排泄情况。本研究前四个部分的研究成果已发表。本文描述尿液排泄情况。通过气相色谱 - 质谱联用仪（GC-MS）对11名男性人体受试者单次服用海洛因后收集的920份尿液样本中的总吗啡（Tmor）、游离吗啡（Fmor）和6 - 乙酰吗啡（6 - AM）进行测定。8人静脉注射3、6和12毫克盐酸海洛因，4人吸食3.5、5.2、7、10.5或13.9毫克海洛因（碱）。此外，向研究样本中添加了183份基于尿液的盲法质量控制样本以评估分析性能。每个样本还采用比色法测定肌酐。所研究的参数与给药途径无显著相关性。Tmor的排泄半衰期均值±标准差为3.11±0.30小时。较低剂量（≤7毫克）给药后，Tmor的尿峰浓度范围（中位数）、达峰时间、低截断值（300纳克/毫升）和高截断值（2000纳克/毫升）下最后阳性样本时间分别为1392 - 9250（3620）纳克/毫升、1.2 - 6.2（2.3）小时、7.4 - 31.9（7.4）小时和0 - 10.1（4.3）小时。较高剂量（>10毫克）给药后，上述参数分别为2065 - 29,030（16,470）纳克/毫升、2.3 - 9.3（4.5）小时、10.7 - 53.5（34.4）小时、2.3 - 22.3（8.3）小时。Fmor与Tmor在同一样本中达峰。低剂量和高剂量下，Fmor峰浓度范围（中位数）及以100纳克/毫升为截断值时最后阳性样本时间分别为117 - 1160（415）纳克/毫升、1.2 - 10.1（4.5）小时和150 - 2580（1400）纳克/毫升、2.3 - 29.1（9.3）小时。6 - AM的尿峰浓度范围（中位数）为6.1 - 568（124）纳克/毫升。一般来说，首次排尿时6 - AM浓度最高，且是唯一在10纳克/毫升截断值时呈阳性的样本。如先前报道，给药后不同受试者之间以及同一受试者不同时间的尿液浓度差异很大，但以每单位肌酐的药物量报告数值时，其可预测性更强。以Tmor形式排泄到尿液中的海洛因百分比范围（中位数）为12.8 - 88.5%（51.0）。
