Service de Pharmacologie Clinique et Pharmacovigilance, Hôpital de la Timone.
Aix Marseille Université, Institut de Neurosciences des Systèmes, Aix-Marseille University, The I nstitut de N eurosciences des S ystèmes.
Ther Drug Monit. 2021 Aug 1;43(4):570-576. doi: 10.1097/FTD.0000000000000836.
Therapeutic drug monitoring of hydroxychloroquine (HCQ) has been recommended to optimize the treatment of patients with COVID-19. The authors describe an ultrahigh-performance liquid chromatography tandem spectrometry method developed in a context of emergency, to analyze HCQ in both human plasma and blood samples. After adding the labeled internal standard and simple protein precipitation, plasma samples were analyzed using a C18 column. Blood samples required evaporation before analysis. The total chromatographic run time was 4 minutes (including 1.5 minutes of column equilibration). The assay was linear over the calibration range (r2 > 0.99) and up to 1.50 mcg/mL for the plasma samples (5.00 mcg/mL for the blood matrix). The limit of quantification was 0.0150 mcg/mL for plasma samples (0.05 mcg/mL blood matrix) with accuracy and precision ranging from 91.1% to 112% and from 0.750% to 11.1%, respectively. Intraday and interday precision and accuracy values were within 15.0%. No significant matrix effect was observed in the plasma or blood samples. This method was successfully applied to patients treated for COVID-19 infection. A simple and rapid ultrahigh-performance liquid chromatography tandem spectrometry method adapted to HCQ therapeutic drug monitoring in the context of SARS-CoV-2 infection was successfully developed and validated.
羟氯喹（HCQ）的治疗药物监测已被推荐用于优化 COVID-19 患者的治疗。作者描述了一种在紧急情况下开发的超高效液相色谱串联质谱法，用于分析人血浆和血液样本中的 HCQ。加入标记的内标和简单的蛋白质沉淀后，使用 C18 柱分析血浆样品。血液样品在分析前需要蒸发。总色谱运行时间为 4 分钟（包括 1.5 分钟的柱平衡）。该测定法在校准范围内呈线性（r2>0.99），血浆样品的上限为 1.50 mcg/mL（血液基质的 5.00 mcg/mL）。血浆样品的定量下限为 0.0150 mcg/mL（血液基质的 0.05 mcg/mL），准确度和精密度范围分别为 91.1%至 112%和 0.750%至 11.1%。日内和日间精密度和准确度值均在 15.0%以内。在血浆或血液样本中未观察到明显的基质效应。该方法已成功应用于治疗 COVID-19 感染的患者。成功开发并验证了一种适用于 SARS-CoV-2 感染背景下 HCQ 治疗药物监测的简单快速的超高效液相色谱串联质谱法。
