Oyler J M, Cone E J, Joseph R E, Huestis M A
Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA.
J Anal Toxicol. 2000 Oct;24(7):530-5. doi: 10.1093/jat/24.7.530.
Allegations of illicit hydrocodone use have been made against individuals who were taking physician-prescribed oral codeine but denied hydrocodone use. Drug detection was based on positive urine opiate immunoassay results with subsequent confirmation of hydrocodone by gas chromatography-mass spectrometry (GC-MS). In these cases, low concentrations of hydrocodone (approximately 100 ng/mL) were detected in urine specimens containing high concentrations of codeine (> 5000 ng/mL). Although hydrocodone has been reported to be a minor metabolite of codeine in humans, there has been little study of this unusual metabolic pathway. We investigated the occurrence of hydrocodone excretion in urine specimens of subjects who were administered codeine. In a controlled study, two African-American and three Caucasian male subjects were orally administered 60 mg/70 kg/day and 120 mg/70 kg/day of codeine sulfate on separate days. Urine specimens were collected prior to and for approximately 30-40 h following drug administration. In a second case study, a postoperative patient self-administered 960 mg/day (240 mg four times per day) of physician-prescribed oral codeine phosphate, and urine specimens were collected on the third day of the dosing regimen. Samples from both studies were extracted on copolymeric solid-phase columns and analyzed by GC-MS. In the controlled study, codeine was detected in the first post-drug-administration specimen from all subjects. Peak concentrations appeared at 2-5 h and ranged from 1475 to 61,695 ng/mL. Codeine was detected at concentrations above the 10-ng/mL limit of quantitation for the assay throughout the 40-h collection period. Hydrocodone was initially detected at 6-11 h following codeine administration and peaked at 10-18 h (32-135 ng/mL). Detection times for hydrocodone following oral codeine administration ranged from 6 h to the end of the collection period. Confirmation of hydrocodone in a urine specimen was always accompanied by codeine detection. Codeine and hydrocodone were detected in all specimens collected from the postoperative patient, and concentrations ranged from 2099 to 4020 and 47 to 129 ng/mL, respectively. Analyses of the codeine formulations administered to subjects revealed no hydrocodone present at the limit of detection of the assay (10 ng/mL). These data confirm that hydrocodone can be produced as a minor metabolite of codeine in humans and may be excreted in urine at concentrations as high as 11% of parent drug concentration. Consequently, the detection of minor amounts of hydrocodone in urine containing high concentrations of codeine should not be interpreted as evidence of hydrocodone abuse.
有人指控一些正在服用医生开的口服可待因但否认使用氢可酮的人非法使用氢可酮。药物检测基于尿液阿片免疫分析结果呈阳性，随后通过气相色谱 - 质谱联用仪（GC - MS）确认氢可酮。在这些案例中，在含有高浓度可待因（> 5000 ng/mL）的尿液样本中检测到低浓度的氢可酮（约100 ng/mL）。尽管据报道氢可酮是可待因在人体内的一种次要代谢产物，但对这种不寻常代谢途径的研究很少。我们调查了服用可待因的受试者尿液样本中氢可酮的排泄情况。在一项对照研究中，两名非裔美国男性和三名白人男性受试者在不同日期分别口服60 mg/70 kg/天和120 mg/70 kg/天的硫酸可待因。在给药前及给药后约30 - 40小时收集尿液样本。在第二个案例研究中，一名术后患者自行服用医生开的口服磷酸可待因，剂量为960 mg/天（每天4次，每次240 mg），并在给药方案的第三天收集尿液样本。两项研究的样本均在共聚固相柱上进行萃取，并通过GC - MS分析。在对照研究中，所有受试者给药后的首个尿液样本中均检测到可待因。峰值浓度出现在2 - 5小时，范围为1475至61695 ng/mL。在整个40小时的收集期内，可待因的检测浓度均高于该检测方法10 ng/mL的定量下限。氢可酮最初在服用可待因后6 - 11小时被检测到，在10 - 18小时达到峰值（32 - 135 ng/mL）。口服可待因后氢可酮的检测时间范围为6小时至收集期结束。尿液样本中氢可酮的确认总是伴随着可待因的检测。从术后患者收集的所有样本中均检测到可待因和氢可酮，浓度分别为2099至4020 ng/mL和47至129 ng/mL。对受试者服用的可待因制剂进行分析，在该检测方法的检测限（10 ng/mL）下未发现氢可酮。这些数据证实氢可酮可作为可待因在人体内的次要代谢产物产生，并可能以高达母体药物浓度11%的浓度排泄到尿液中。因此，在含有高浓度可待因的尿液中检测到少量氢可酮不应被解释为氢可酮滥用的证据。
