Development and Validation of an Improved HPLC-MS/MS Method for Quantifying Total and Unbound Lenalidomide in Human Plasma.

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmaceutics Pub Date : 2024-10-19 DOI:10.3390/pharmaceutics16101340

Suhyun Lee, Seungwon Yang, Wang-Seob Shim, Eunseo Song, Seunghoon Han, Sung-Soo Park, Suein Choi, Sung Hwan Joo, Seok Jun Park, Beomjin Shin, Donghyun Kim, Hyeonsu Kim, Yujung Jung, Kyung-Tae Lee, Eun Kyoung Chung

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引用次数: 0

Abstract

Background/objectives: This study aimed to develop a fully validated HPLC-MS/MS method for quantifying total and unbound lenalidomide concentrations in human plasma.

Methods: Unbound concentrations were measured using plasma ultrafiltrate prepared with Amicon^® Centrifugal Filters. Lenalidomide and lenalidomide-d5 (internal standard) were extracted from 50 μL of human plasma using liquid-liquid extraction. Chromatography was conducted with a Halo^® C18 column using 0.1% formic acid and methanol (20:80, v/v) as the mobile phase. The mass spectrometer was operated in a positive ion mode with an electrospray ionization interface and multiple reaction monitoring modes.

Results: Calibration curves were linear over the range of 5 to 1000 ng/mL (r² > 0.996) for both the total and unbound lenalidomide. For total lenalidomide concentrations, between-run precision (coefficients of variation) and accuracy were 1.70-7.65% and 94.45-101.10%, respectively. For unbound concentrations, inter-day precision and accuracy were 1.98-10.55% and 93.95-98.48%, respectively.

Conclusions: We developed a highly reproducible, sensitive, and efficient bioanalytical method using a smaller volume of plasma sample (50 μL) with a relatively short run time (2.5 min). The proposed analytical method was successfully applied to measure total and unbound lenalidomide concentrations at various time points in multiple myeloma patients with renal impairment.

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开发和验证用于定量人血浆中来那度胺总量和未结合量的改进型 HPLC-MS/MS 方法

背景/目的：本研究旨在开发一种经过充分验证的 HPLC-MS/MS 方法，用于定量检测人体血浆中来那度胺的总浓度和未结合浓度：使用Amicon®离心过滤器制备的血浆超滤液测量非结合浓度。来那度胺和来那度胺-d5（内标）采用液液萃取法从50微升人体血浆中提取。色谱采用 Halo® C18 色谱柱，以 0.1% 甲酸和甲醇（20:80, v/v）为流动相。质谱仪采用电喷雾离子化界面的正离子模式和多重反应监测模式：来那度胺总浓度和未结合浓度在5至1000 ng/mL范围内线性关系良好（r2 > 0.996）。来那度胺总浓度的运行间精密度（变异系数）和准确度分别为1.70%-7.65%和94.45%-101.10%。未结合浓度的日间精密度和准确度分别为1.98-10.55%和93.95-98.48%：我们开发了一种重现性高、灵敏度高且高效的生物分析方法，使用的血浆样品量较小（50 μL），运行时间相对较短（2.5 分钟）。所提出的分析方法成功地用于测定肾功能受损的多发性骨髓瘤患者在不同时间点的来那度胺总浓度和未结合浓度。

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来源期刊

Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

7.90

自引率

11.10%

发文量

2379

审稿时长

16.41 days

期刊介绍： Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications, and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.