Couto Joseph E, Webster Lynn, Romney Martha C, Leider Harry L, Linden Ariel
Jefferson School of Population Health, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
J Opioid Manag. 2009 Nov-Dec;5(6):359-64. doi: 10.5055/jom.2009.0035.
This study examined the ability of an algorithm applied to urine drug levels of oxycodone in healthy adult volunteers to differentiate among low, medium, and high doses of OxyContin.
Thirty-six healthy volunteers were randomized to receive 80, 160, or 240 mg of daily OxyContin to steady state while under a naltrexone blockade. During days 3 and 4 of the study, urine samples of all participants were collected, and oxycodone levels detected in the urine were obtained using a liquid chromatography-mass spectrometry (LC-MS-MS) assay.
The concordance was calculated for raw and adjusted LC-MS-MS urine oxycodone values within each study participant between their third and fourth day values. Also, an analysis of medians was calculated for each of the dosage groupings using Bonett-Price confidence intervals for both raw and adjusted LC-MS-MS values.
The concordance correlation coefficient for the raw LC-MS-MS values between days 3 and 4 was 0.689 (95% confidence intervals = 0.515, 0.864), whereas the concordance correlation coefficient for the LC-MS-MS values using the algorithm (ie, normalized values) was 0.882 (95% confidence intervals = 0.808, 0.956). Because of greater variability in the raw values, some overlap was observed in the confidence intervals of the various OxyContin doses, whereas no overlap was observed in the normalized confidence intervals regardless of the application of a Bonferroni adjustment.
In contrast to raw LC-MS-MS values, an algorithm that normalizes oxycodone urine drug levels for pH, specific gravity, and lean body mass discriminates well among all three of the daily doses of OxyContin tested (80, 160, and 240 mg), even with correcting for multiple analyses.
本研究考察了一种应用于健康成年志愿者尿液中羟考酮药物水平的算法区分低、中、高剂量奥施康定的能力。
36名健康志愿者被随机分组,在纳曲酮阻滞作用下接受每日80、160或240毫克奥施康定直至达到稳态。在研究的第3天和第4天,收集所有参与者的尿液样本,并使用液相色谱 - 质谱联用(LC - MS - MS)分析法测定尿液中检测到的羟考酮水平。
计算每个研究参与者第3天和第4天原始及校正后的LC - MS - MS尿液羟考酮值之间的一致性。此外,使用Bonett - Price置信区间对原始及校正后的LC - MS - MS值分别计算每个剂量分组的中位数分析。
第3天和第4天原始LC - MS - MS值的一致性相关系数为0.689(95%置信区间 = 0.515, 0.864),而使用该算法(即归一化值)的LC - MS - MS值的一致性相关系数为0.882(95%置信区间 = 0.808, 0.956)。由于原始值的变异性更大,在各种奥施康定剂量的置信区间中观察到一些重叠,而无论是否应用Bonferroni校正,在归一化置信区间中均未观察到重叠。
与原始LC - MS - MS值相比,一种针对pH、比重和瘦体重对羟考酮尿液药物水平进行归一化的算法,即使在进行多次分析校正后,也能很好地区分所测试的所有三种每日剂量的奥施康定(80、160和240毫克)。