Pesce Amadeo, West Cameron, West Robert, Crews Bridgit, Mikel Charles, Rosenthal Murray, Almazon Perla, Latyshev Sergey
Millennium Research Institute, San Diego, California, USA.
J Opioid Manag. 2011 Mar-Apr;7(2):117-22. doi: 10.5055/jom.2011.0054.
Clinical laboratories are required to establish reference intervals for all the analytes tested, and these are provided along with the test results. In contrast, laboratories testing for pain medications use cutoffs established by the manufacturers of immunoassay reagents. These cutoffs may be inappropriate for monitoring patients being treated for chronic pain with opioid therapy because the cutoffs are set too high.
To use quantitative urine drug excretion data determined by liquid chromatography-tandem mass spectrometry analysis to calculate cutoffs needed to best determine patient compliance with prescribed medications.
Two methods of calculation were used to estimate cutoffs. First, all positive results for each drug or drug metabolite were ranked from highest to lowest. The lowest value was one-half of the lower limit of quantitation. A nonparametric 2.5 percent estimator was used to establish each cutoff Second, positive results were normalized using creatinine values, resulting in the excretion being expressed as nanograms of excreted drug per gram of creatinine. A nonparametric 2.5 percent estimator was used to establish the cutoff.
Cutoffs established using these calculations included at least 97.5 percent of the data for the drugs: 7-aminoclonazepam, alpha-hydroxalprazolam, buprenorphine, carisoprodol, hydrocodone, hydromorphone, meperidine, meprobamate, methadone, morphine, oxycodone, oxymorphone, propoxyphene, and tramadol gave cutoffs near the lower limit of quantitation. One exception was with the drug codeine, where the lower limit could not be identified.
These cutoffs were significantly lower than those suggested by many immunoassay manufacturers and better identify patient compliance in a representative population of pain patients. The limitation of the study is that only values one-half of our lowest calibrator were used. By using population values, laboratories can establish appropriate cutoffs for best monitoring pain patient medication compliance.
临床实验室需要为所有检测的分析物建立参考区间，并将其与检测结果一同提供。相比之下，检测止痛药物的实验室使用免疫分析试剂制造商设定的临界值。这些临界值可能不适用于监测接受阿片类药物治疗慢性疼痛的患者，因为临界值设定得过高。
利用液相色谱 - 串联质谱分析测定的定量尿液药物排泄数据来计算最能确定患者对处方药依从性所需的临界值。
使用两种计算方法来估计临界值。首先，将每种药物或药物代谢物的所有阳性结果从最高到最低排序。最低值为定量下限的一半。使用非参数2.5%估计器来确定每个临界值。其次，使用肌酐值对阳性结果进行标准化，使排泄量表示为每克肌酐排泄药物的纳克数。使用非参数2.5%估计器来确定临界值。
使用这些计算方法确定的临界值包含至少97.5%的药物数据：7 - 氨基氯硝西泮、α - 羟基阿普唑仑、丁丙诺啡、卡立普多、氢可酮、氢吗啡酮、哌替啶、甲丙氨酯、美沙酮、吗啡、羟考酮、奥施康定、丙氧芬和曲马多的临界值接近定量下限。一个例外是可待因药物，其下限无法确定。
这些临界值显著低于许多免疫分析制造商建议的临界值，并且能更好地在有代表性的疼痛患者群体中确定患者的依从性。该研究的局限性在于仅使用了最低校准品一半的值。通过使用群体值，实验室可以建立适当的临界值，以最佳地监测疼痛患者的药物依从性。
