Development and Validation of the LC–MS/MS Method and Its Application for Pharmacokinetic Studies for the Simultaneous Estimation of Motixafortide and Filgrastim in rat Plasma

IF 1.8 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS

Biomedical Chromatography Pub Date : 2025-05-26 DOI:10.1002/bmc.70126

Lurdhu Mary K, Naresh Podila, Afzal B. Shaik, Jithendra Chimakurthy

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引用次数: 0

Abstract

Introduction

Motixafortide, a CXCR4 antagonist, and filgrastim, a granulocyte colony-stimulating factor, have shown significant potential in enhancing hematopoietic stem cell mobilization and improving cancer treatment outcomes when used in combination. However, critical challenges persist due to the absence of analytical methods and the necessity for reliable quantification of both drugs in biological matrices. This research aims to address these gaps by developing and validating a liquid chromatography–tandem mass spectrometry method for the simultaneous quantification of motixafortide and filgrastim in rat plasma.

Experiment

An isocratic mobile phase with acetonitrile and buffer was employed for separation, following protein precipitation with acetonitrile, using a C₁₈ Waters X-Terra RP-18 column (150x4.6 mm,3.5 μm). Liquid chromatography–tandem mass spectrometry with an internal standard employs multiple reaction monitoring in electrospray ionization (positive ion mode) to monitor the transitions. The method was validated according to USFDA guidelines, assessing parameters such as selectivity, matrix effect, linearity, precision, accuracy, lower limit of quantification, and stability.

Results

This method was successfully applied in pharmacokinetic studies, ensuring reliable and accurate quantification of co-administered motixafortide and filgrastim. These findings significantly contribute to optimizing therapeutic protocols and enhancing treatment outcomes for cancer patients.

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大鼠血浆中莫替福肽和非格拉西汀同时测定的LC-MS /MS方法的建立、验证及其药动学研究

Motixafortide（一种CXCR4拮抗剂）和非格昔汀（一种粒细胞集落刺激因子）联合使用时，已显示出增强造血干细胞动员和改善癌症治疗效果的显著潜力。然而，由于缺乏分析方法和对生物基质中两种药物进行可靠定量的必要性，关键的挑战仍然存在。本研究旨在通过建立和验证液相色谱-串联质谱同时定量大鼠血浆中莫替福肽和非格拉西汀的方法来解决这些空白。实验采用乙腈和缓冲液等容流动相分离，乙腈沉淀蛋白质，色谱柱为C18 Waters X-Terra RP-18 （150 × 4.6 mm,3.5 μm）。内标液相色谱-串联质谱法采用电喷雾电离（正离子模式）下的多重反应监测来监测转变。根据USFDA指南对该方法进行了验证，评估了选择性、基质效应、线性、精密度、准确度、定量下限和稳定性等参数。结果该方法可用于药动学研究，保证了莫替福肽与非格拉西汀合用的定量可靠、准确。这些发现有助于优化治疗方案，提高癌症患者的治疗效果。

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

Biomedical Chromatography 生物-分析化学

CiteScore

3.60

自引率

5.60%

发文量

268

审稿时长

2.3 months

期刊介绍： Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.