Validation of an LC–MS/MS method for quantitation of fostemsavir in plasma

IF 1.3 4区医学 Q4 PHARMACOLOGY & PHARMACY

Journal of pharmacological and toxicological methods Pub Date : 2023-03-01 DOI:10.1016/j.vascn.2023.107254

Siddhartha Lolla , Kumar Shiva Gubbiyappa , Shankar Cheruku , D.V.R.N. Bhikshapathi

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引用次数: 1

Abstract

Background

A novel, sensitive and specific LC-MS/MS technique was developed and validated for the quantification of fostemsavir in human plasma and its pharmacokinetic application in rabbits.

Methods

Chromatographic separation of the fostemsavir and fosamprenavir (internal standard) were achieved on Zorbax C18 (50 mm × 2 mm × 5 μm) column with 0.80 mL/min flow rate and coupled with API6000 triple quadrupole MS in multi reaction monitoring mode by applying mass transitions m/z 584.16/105.03 for fostemsavir and m/z 586.19/57.07 for the internal standard.

Results

The calibration curve exhibited linearity in concentration range of 58.5–2340.0 ng/mL for fostemsavir. The LLOQ was 58.5 ng/mL. The validated LC–MS/MS process was effectively applied for the analysis of plasma in healthy rabbits for determinations of Fostemsavir. From the pharmacokinetic data, the mean of C_max and T_max were 198.19 ± 5.85 ng/mL and 2.42 ± 0.13, respectively. Plasma concentration reduced with t_1/2 of 7.02 ± 0.14. AUC_0→Last value obtained was 2374.87 ± 29.75 ng. h/ml, respectively.

Conclusion

In summary, the developed method has been successfully validated and pharmacokinetic parameters were demonstrated after oral administration of Fostemsavir to healthy rabbits.

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液相色谱-质谱联用法测定血浆中fostemsavir含量的验证

建立了一种新的、灵敏的、特异的LC-MS/MS技术，并验证了其在兔体内的药代动力学应用。方法采用Zorbax C18 (50 mm × 2 mm × 5 μm)色谱柱，流速为0.80 mL/min，采用API6000三极四极质谱联用，以m/z 584.16/105.03和m/z 586.19/57.07为质谱谱，采用多反应监测模式对fostemsavir和fosamprenavir(内标)进行色谱分离。结果本品在58.5 ~ 2340.0 ng/mL范围内具有良好的线性关系。定量限为58.5 ng/mL。经验证的LC-MS /MS方法可有效地用于健康家兔血浆中Fostemsavir的测定。药动学数据显示，Cmax和Tmax的平均值分别为198.19±5.85 ng/mL和2.42±0.13 ng/mL。血药浓度随t1/2(7.02±0.14)降低。AUC0→最后值为2374.87±29.75 ng。分别h /毫升。结论本研究成功验证了该方法的有效性，并对健康家兔口服fostemsaver后的药动学参数进行了验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY

CiteScore

3.60

自引率

10.50%

发文量

审稿时长

26 days

期刊介绍： Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.