Westra Niels, van Hateren Kai, Kosterink Jos G W, Lub-de Hooge Marjolijn N, Oude Munnink Thijs H, Touw Daan J
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
PharmacoTherapy, Epidemiology & Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
Biomed Chromatogr. 2025 Sep;39(9):e70179. doi: 10.1002/bmc.70179.
Measuring cobicistat and venetoclax concentrations in human plasma and serum facilitates therapeutic drug monitoring (TDM) and pharmacokinetic (PK) boosting studies. Therefore, the objective of this study was to develop and validate a rapid LC-MS/MS analytical method for the simultaneous determination of cobicistat and venetoclax concentrations in plasma and serum. The method was validated according to EMA and FDA guidelines. Chromatographic separation was performed using a liquid chromatography (LC) system with a C18 column. The elution gradient involved two mobile phases: mobile phase A (ammonium formate) and mobile phase B (acetonitrile). The concentration range was 5-500 μg/L for cobicistat and 50-5000 μg/L for venetoclax. Accuracy and precision were within the required limits, with accuracy ranging from -5.9% to 2.4%, within-day precision from 1.2% to 4.8%, and between-day precision from 0.4% to 4.3%. Cobicistat and venetoclax were stable for at least 8 days under various storage and handling conditions. Clinical TDM samples showed mean concentrations ± standard deviation (SD) of 138.8 ± 123.3 μg/L for cobicistat and 1497.1 ± 1285.9 μg/L for venetoclax. The development and validation of this LC-MS/MS assay provide a reliable and efficient method for the simultaneous quantification of cobicistat and venetoclax in plasma and serum samples.
测定人血浆和血清中的考比司他和维奈托克浓度有助于治疗药物监测（TDM）和药代动力学（PK）增强研究。因此，本研究的目的是开发并验证一种快速液相色谱-串联质谱（LC-MS/MS）分析方法，用于同时测定血浆和血清中的考比司他和维奈托克浓度。该方法根据欧洲药品管理局（EMA）和美国食品药品监督管理局（FDA）的指南进行了验证。使用配备C18柱的液相色谱（LC）系统进行色谱分离。洗脱梯度涉及两种流动相：流动相A（甲酸铵）和流动相B（乙腈）。考比司他的浓度范围为5-500μg/L，维奈托克的浓度范围为50-5000μg/L。准确度和精密度在规定限度内，准确度范围为-5.9%至2.4%，日内精密度为1.2%至4.8%，日间精密度为0.4%至4.3%。考比司他和维奈托克在各种储存和处理条件下至少稳定8天。临床TDM样本显示，考比司他的平均浓度±标准差（SD）为138.8±123.3μg/L，维奈托克的平均浓度±标准差为1497.1±1285.9μg/L。这种LC-MS/MS测定方法的开发和验证为同时定量血浆和血清样本中的考比司他和维奈托克提供了一种可靠且高效的方法。
