Hendrikx Jeroen J M A, Rosing Hilde, Schinkel Alfred H, Schellens Jan H M, Beijnen Jos H
Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands; Division of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Biomed Chromatogr. 2014 Feb;28(2):302-10. doi: 10.1002/bmc.3021. Epub 2013 Aug 29.
A combined assay for the determination of paclitaxel, docetaxel and ritonavir in human feces and urine is described. The drugs were extracted from 200 μL urine or 50 mg feces followed by high-performance liquid chromatography analysis coupled with positive ionization electrospray tandem mass spectrometry. The validation program included calibration model, accuracy and precision, carry-over, dilution test, specificity and selectivity, matrix effect, recovery and stability. Acceptance criteria were according to US Food and Drug Administration guidelines on bioanalytical method validation. The validated range was 0.5-500 ng/mL for paclitaxel and docetaxel, 2-2000 ng/mL for ritonavir in urine, 2-2000 ng/mg for paclitaxel and docetaxel, and 8-8000 ng/mg for ritonavir in feces. Inter-assay accuracy and precision were tested for all analytes at four concentration levels and were within 8.5% and <10.2%, respectively, in both matrices. Recovery at three concentration levels was between 77 and 94% in feces samples and between 69 and 85% in urine samples. Method development, including feces homogenization and spiking blank urine samples, are discussed. We demonstrated that each of the applied drugs could be quantified successfully in urine and feces using the described assay. The method was successfully applied for quantification of the analytes in feces and urine samples of patients.
本文描述了一种用于测定人粪便和尿液中紫杉醇、多西他赛和利托那韦的联合检测方法。从200 μL尿液或50 mg粪便中提取药物，然后进行高效液相色谱分析，并结合正离子电喷雾串联质谱法。验证程序包括校准模型、准确度和精密度、残留、稀释试验、特异性和选择性、基质效应、回收率和稳定性。验收标准依据美国食品药品监督管理局生物分析方法验证指南。验证范围为尿液中紫杉醇和多西他赛为0.5 - 500 ng/mL，利托那韦为2 - 2000 ng/mL；粪便中紫杉醇和多西他赛为2 - 2000 ng/mg，利托那韦为8 - 8000 ng/mg。在两种基质中，对所有分析物在四个浓度水平进行了批间准确度和精密度测试，分别在8.5%以内和<10.2%以内。粪便样品中三个浓度水平的回收率在77%至94%之间，尿液样品中在69%至85%之间。讨论了方法开发，包括粪便匀浆和向空白尿液样品中加样。我们证明，使用所描述的检测方法可以成功地对尿液和粪便中的每种应用药物进行定量。该方法已成功应用于患者粪便和尿液样品中分析物的定量。
