Johnson-Davis Kamisha L
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT.
ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT.
J Appl Lab Med. 2018 Jan 1;2(4):564-572. doi: 10.1373/jalm.2016.022947.
Opiates/opioids and benzodiazepines are commonly prescribed drug therapies for acute and chronic pain. Urine drug testing is often employed to assess adherence to these mediations. Opioids and benzodiazepines are drug classes that undergo extensive metabolism through glucuronidation/sulfation. Conjugated glucuronide and sulfate drug metabolites can be difficult to detect by immunoassay and mass spectrometry methods. Consequently, false-negative or false-positive results can have a damaging impact on patient care. A common dilemma among drug-testing laboratories is whether to perform preanalytical hydrolysis to increase detection of drugs that are highly conjugated as metabolites.
The purpose of hydrolysis is to cleave the glucuronide or sulfate compounds to enhance analyte detection by increasing the parent drug concentration of those drugs that are primarily metabolized by glucuronidation or sulfation. Hydrolysis procedures can be performed by acid, base, or enzyme sources (β-glucuronidase).
Preanalytical hydrolysis can improve the overall detection of most opioids and benzodiazepine drugs. However, the limitation of this procedure is that the process can be time-consuming and prolong the turnaround time to result. In addition, chemical hydrolysis has the potential to degrade opioid and benzodiazepine drugs, whereas incomplete hydrolysis and variable hydrolysis efficiencies can occur with an enzymatic approach.
Preanalytical hydrolysis can improve the sensitivity of drug detection for drug classes such as opiates/opioids and benzodiazepines, which are highly metabolized by glucuronidation and sulfation and should be implemented in analytical procedures to convert conjugated metabolites into the free (unbound) form.
阿片类药物和苯二氮䓬类药物是常用于急性和慢性疼痛治疗的药物疗法。尿液药物检测常被用于评估患者对这些药物的依从性。阿片类药物和苯二氮䓬类药物是通过葡萄糖醛酸化/硫酸化进行广泛代谢的药物类别。结合型葡萄糖醛酸和硫酸药物代谢物可能难以通过免疫测定法和质谱法检测到。因此,假阴性或假阳性结果可能会对患者护理产生不利影响。药物检测实验室常见的一个两难问题是是否进行分析前水解,以增加对作为代谢物高度结合的药物的检测。
水解的目的是裂解葡萄糖醛酸或硫酸化合物,通过增加主要通过葡萄糖醛酸化或硫酸化代谢的药物的母体药物浓度来提高分析物的检测。水解程序可以通过酸、碱或酶源(β-葡萄糖醛酸酶)进行。
分析前水解可以提高大多数阿片类药物和苯二氮䓬类药物的总体检测率。然而,该程序的局限性在于过程可能耗时并延长结果周转时间。此外,化学水解有可能降解阿片类药物和苯二氮䓬类药物,而酶促方法可能会出现水解不完全和水解效率可变的情况。
分析前水解可以提高对阿片类/阿片样物质和苯二氮䓬类等药物类别的药物检测灵敏度,这些药物通过葡萄糖醛酸化和硫酸化进行高度代谢,应在分析程序中实施,以将结合型代谢物转化为游离(未结合)形式。