Wu Fang, Marin Stephanie J, McMillin Gwendolyn A
Department of Pathology, University of Utah, Salt Lake City, UT 84132, USA.
ARUP Laboratories, 500 Chipeta Way, MS-115, Salt Lake City, UT 84108, USA.
J Anal Toxicol. 2017 Apr 1;41(3):196-204. doi: 10.1093/jat/bkw113.
In this study, the stability of 21 cocaine, opioid and benzodiazepine analytes in spiked meconium was investigated at three storage temperatures: 4°C, room temperature (RT), and 37°C (body temperature). The drugs/metabolites included were hydrocodone, hydromorphone, codeine, morphine, 6-acetylmorphine (6-AM), oxycodone, oxymorphone, cocaine, cocaethylene, benzoylecgonine, m-hydroxybenzoylecgonine, diazepam, oxazepam, temazepam, nordiazepam, chlordiazepoxide, lorazepam, alprazolam, alpha-hydroxyalprazolam, clonazepam, 7-aminoclonazepam, midazolam, alpha-hydroxymidazolam and zolpidem. Drug testing was performed using mass spectrometry methods that were validated for clinical use. After 2 weeks of storage, a substantial loss was observed in the concentrations of 7-aminoclonazepam (48.4% at 4°C and 71.5% at RT), and chlordiazepoxide (59.5% at RT). A slight decrease was observed in the concentrations of alprazolam (20.9% at 4°C), clonazepam (24.5% at 4°C), chlordiazepoxide (23.5% at 4°C), midazolam (20.8% at 4°C), nordiazepam (22.8% at RT), and alpha-hydroxyalprazolam (20.7% at 4°C). At 37°C, the concentrations of chlordiazepoxide, 7-aminoclonazepam, lorazepam, oxazepam, nordiazepam and temazepam decreased by 81.4%, 86.8%, 56.5%, 59.9%, 45.4% and 31.7%, respectively, after 2 weeks. 6-AM was observed to be unstable regardless of storage temperatures. For morphine, a 33.3% increase at 4°C and a 23.4% increase at RT were observed after 2 weeks, respectively, possibly due to 6-AM degradation, while no changes ≥20% were observed at 37°C. All other analytes were stable up to 2 weeks at all three storage temperatures (concentration changes <20%). The stability of select drug analytes in authentic clinical meconium specimens was consistent with that observed in spiked meconium. In conclusion, some drugs in meconium may not be stable for long periods of time. Sample storage conditions are an important consideration in the context of detection windows and interpreting drug-testing results in meconium. To the best of our knowledge, this is the first stability study of cocaine, opioids and benzodiazepines in meconium concerning the effects of storage temperatures.
在本研究中,对21种可卡因、阿片类药物和苯二氮䓬类分析物在添加到胎粪中的情况下,于三个储存温度(4°C、室温(RT)和37°C(体温))下的稳定性进行了研究。所包括的药物/代谢物有氢可酮、氢吗啡酮、可待因、吗啡、6 - 乙酰吗啡(6 - AM)、羟考酮、羟吗啡酮、可卡因、可口卡因、苯甲酰爱康宁、间羟基苯甲酰爱康宁、地西泮、奥沙西泮、替马西泮、去甲地西泮、氯氮卓、劳拉西泮、阿普唑仑、α - 羟基阿普唑仑、氯硝西泮、7 - 氨基氯硝西泮、咪达唑仑、α - 羟基咪达唑仑和唑吡坦。使用经临床验证的质谱方法进行药物检测。储存2周后,观察到7 - 氨基氯硝西泮(4°C时损失48.4%,室温时损失71.5%)和氯氮卓(室温时损失59.5%)的浓度大幅下降。阿普唑仑(4°C时下降20.9%)、氯硝西泮(4°C时下降24.5%)、氯氮卓(4°C时下降23.5%)、咪达唑仑(4°C时下降20.8%)、去甲地西泮(室温时下降22.8%)和α - 羟基阿普唑仑(4°C时下降20.7%)的浓度略有下降。在37°C下,储存2周后,氯氮卓、7 - 氨基氯硝西泮、劳拉西泮、奥沙西泮、去甲地西泮和替马西泮的浓度分别下降了81.4%、86.8%、56.5%、59.9%、45.4%和31.7%。无论储存温度如何,均观察到6 - AM不稳定。对于吗啡,储存2周后,4°C时浓度增加33.3%,室温时增加23.4%,这可能是由于6 - AM降解所致,而在37°C时未观察到≥20%的变化。在所有三个储存温度下,所有其他分析物在长达2周的时间内都是稳定的(浓度变化<20%)。真实临床胎粪标本中选定药物分析物的稳定性与添加到胎粪中的情况一致。总之,胎粪中的一些药物可能长时间不稳定。在检测窗口期以及解释胎粪药物检测结果时,样本储存条件是一个重要的考虑因素。据我们所知,这是关于储存温度对胎粪中可卡因、阿片类药物和苯二氮䓬类稳定性影响的首次研究。