Rezk Naser L, Abdel-Megeed Mohamed F, Kashuba Angela D M
Clinical Pharmacology/Analytical Chemistry Core, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Ther Drug Monit. 2007 Aug;29(4):429-36. doi: 10.1097/FTD.0b013e318074db39.
Understanding the pharmacology of drugs in breast milk is important for the health of both mother and baby. Current methods to measure drug concentrations in breast milk are not easily validated for precision or accuracy, primarily because of suboptimal sample clean-up. We report here an optimized clean-up method to remove both proteins and fat from milk, thereby enhancing the extraction efficiency of antiretroviral drugs. Recoveries were consistently above 91% for all drugs, demonstrating that this method successfully and reliably released drugs from fat globules. With use of 200 muL of human breast milk, an high-performance liquid chromatography/ultraviolet method for simultaneously detecting lamivudine, stavudine, zidovudine, and nevirapine was validated over the range of 20 to 20,000 ng/mL. Intra- and interday precision (average percent relative standard deviation) and accuracy (average percent deviation from nominal) was less than 3.6% and 7.5%, respectively. Intra- and interday accuracy (average percent deviation from nominal) was less than 0.25% and 1.3%, respectively. This novel method efficiently, reliably, and accurately measured antiretroviral drugs in breast milk and can be applied to any matrix containing fat and protein.
了解母乳中药物的药理学对母婴健康都很重要。目前测量母乳中药物浓度的方法在精密度或准确性方面不易得到验证，主要原因是样品净化效果欠佳。我们在此报告一种优化的净化方法，可去除母乳中的蛋白质和脂肪，从而提高抗逆转录病毒药物的提取效率。所有药物的回收率均持续高于91%，表明该方法成功且可靠地从脂肪球中释放出药物。使用200 μL人母乳，一种同时检测拉米夫定、司他夫定、齐多夫定和奈韦拉平的高效液相色谱/紫外方法在20至20,000 ng/mL范围内得到验证。日内和日间精密度（平均相对标准偏差百分比）和准确度（与标称值的平均偏差百分比）分别小于3.6%和7.5%。日内和日间准确度（与标称值的平均偏差百分比）分别小于0.25%和1.3%。这种新方法高效、可靠且准确地测量了母乳中的抗逆转录病毒药物，并且可应用于任何含有脂肪和蛋白质的基质。
