Tarek Mahmoud Sally, Moffid Marwa A, Sayed Rawda M, Mostafa Eman A
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt.
Microchem J. 2022 Oct;181:107769. doi: 10.1016/j.microc.2022.107769. Epub 2022 Jul 15.
A sensitive and selective UPLC-MS/MS method was developed for the synchronized determination of four drugs used in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, azithromycin, apixaban, dexamethasone, and favipiravir in rat plasma. using a Poroshell 120 EC-C18 column (50 mm × 4.6 mm, 2.7 m) with a high-resolution ESI tandem mass spectrometer detection with multiple reaction monitoring. We used an Agilent Poroshell column, which is characterized by a stationary phase based on non-porous core particles. With a remarkable improvement in the number of theoretical plates and low column backpressure. In addition, the developed method was employed in studying the potential food-drug interaction of grapefruit juice (GFJ) with the selected drugs which affects their pharmacokinetics in rats. The LC-MS/MS operated in positive and negative ionization mode using two internal standards: moxifloxacin and chlorthalidone, respectively. Liquid- liquid extraction of the cited drugs from rat plasma was accomplished using diethyl ether: dichloromethane (70:30, ). The analytes were separated using methanol: 0.1 % formic acid in water (95: 5, ) as a mobile phase in isocratic mode of elution pumped at a flow rate of 0.3 mL/min. A detailed validation of the bio-analytical method was performed in accordance with US-FDA and EMA guidelines. Concerning the pharmacokinetic study, the statistical significance between the results of the test groups receiving GFJ along with the cited drugs and the control group was assessed demonstrating that GFJ increased the plasma concentration of azithromycin, apixaban, and dexamethasone. Accordingly, this food-drug interaction requires cautious ingestion of GFJ in patients using (SARS-CoV-2) medications as it can produce negative effects in the safety of the drug therapy. A potential drug-drug interaction is also suggested between those medications requiring a suitable dose adjustment.
开发了一种灵敏且选择性高的超高效液相色谱-串联质谱（UPLC-MS/MS）方法，用于同步测定大鼠血浆中用于治疗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的四种药物，即阿奇霉素、阿哌沙班、地塞米松和法匹拉韦。使用Poroshell 120 EC-C18柱（50 mm×4.6 mm，2.7 µm），并通过高分辨率电喷雾电离（ESI）串联质谱仪进行多反应监测检测。我们使用了安捷伦Poroshell柱，其特点是基于无孔核颗粒的固定相。理论塔板数显著增加，柱背压较低。此外，所开发的方法用于研究葡萄柚汁（GFJ）与所选药物之间潜在的食物-药物相互作用，这种相互作用会影响它们在大鼠体内的药代动力学。LC-MS/MS分别使用两种内标物莫西沙星和氯噻酮在正离子和负离子模式下运行。使用乙醚：二氯甲烷（70:30）从大鼠血浆中液-液萃取上述药物。以甲醇：0.1%甲酸水溶液（95:5）作为流动相，在等度洗脱模式下以0.3 mL/min的流速泵送，对分析物进行分离。按照美国食品药品监督管理局（US-FDA）和欧洲药品管理局（EMA）的指南对生物分析方法进行了详细验证。关于药代动力学研究，评估了接受GFJ与上述药物的试验组结果与对照组结果之间的统计学显著性，结果表明GFJ增加了阿奇霉素、阿哌沙班和地塞米松的血浆浓度。因此，对于使用（SARS-CoV-2）药物的患者，这种食物-药物相互作用需要谨慎摄入GFJ，因为它可能对药物治疗的安全性产生负面影响。还提示了这些药物之间可能存在药物-药物相互作用，需要适当调整剂量。
