Determining Zolpidem Compliance: Urinary Metabolite Detection and Prevalence in Chronic Pain Patients
Determining Zolpidem Compliance: Urinary Metabolite Detection and Prevalence in Chronic Pain Patients
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DOI：
10.1093/jat/bku068
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发表时间：
2014-10-01
影响因子：
2.5
通讯作者：
Heltsley, Rebecca
中科院分区：
文献类型：
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作者：
Schwope, David M.;DePriest, Anne;Heltsley, Rebecca
唑吡坦（Ambien（R））是美国最常用的失眠治疗药物;然而，对唑吡坦代谢物在慢性疼痛患者中的排泄知之甚少。由于唑吡坦在体内广泛代谢为唑吡坦4-苯基羧酸（ZCA），因此代谢物检测可提高依从性测定的准确性，从而改善临床决策。通过混合模式固相萃取从1 mL人尿液中提取唑吡坦和ZCA。通过LC-MS-MS使用正电喷雾电离分析样品，采用多反应监测模式进行检测和定量。梯度色谱分离，实现了快速1.8分钟的分析与反相柱。唑吡坦在4 - 1，000 μ g/L范围内和ZCA在4 - 10，000 μ g/L范围内呈线性。日间回收率（偏倚）和不精密度（n = 20）分别为目标值的100-107%和2.4-3.7%相对标准偏差。萃取效率为78- 90%。对疼痛依从性样本（n = 3，142）进行去识别并分析唑吡坦和ZCA。在720份标本（22.9%）中检测到唑吡坦大于定量限，而在1，579份标本（50.3%）中检测到ZCA。仅5份标本单独含有唑吡坦。在864份标本中观察到ZCA不含母体唑吡坦，从而使群体检出率增加27.5%。将唑吡坦代谢物添加到依从性测定中显著改善了唑吡坦摄入量的检测，并应证明在临床和法医环境中有用。
Zolpidem (Ambien (R)) is the most prescribed insomnia treatment in the USA; however, little is known about zolpidem metabolite excretion in chronic pain patients. As zolpidem is extensively metabolized in vivo to zolpidem 4-phenyl carboxylic acid (ZCA), metabolite detection may provide improved accuracy for compliance determinations, thereby improving clinical decisions. Zolpidem and ZCA were extracted from 1 mL human urine by mixed-mode solid-phase extraction. Samples were analyzed by LC-MS-MS using positive electrospray ionization with multiple reaction monitoring mode employed for detection and quantification. Gradient chromatographic separation was achieved with a reversed-phase column in a rapid 1.8 min analysis. The assay was linear from 4 to 1,000 mu g/L for zolpidem and 4 to 10,000 mu g/L for ZCA. Interday recovery (bias) and imprecision (n = 20) were 100-107% of target and 2.4-3.7% relative standard deviation, respectively. Extraction efficiencies were 78-90%. Pain compliance samples (n = 3,142) were de-identified and analyzed for zolpidem and ZCA. Zolpidem was detected greater than limit of quantification in 720 specimens (22.9%), while ZCA was detected in 1,579 specimens (50.3%). Only five specimens contained zolpidem alone. ZCA was observed without parent zolpidem in 864 specimens, thereby increasing population detection rates by 27.5%. Addition of a zolpidem metabolite to compliance determinations substantially improved detection for zolpidem intake and also should prove useful in clinical and forensic settings.