Determination of free and total vincristine in human plasma after intravenous administration of vincristine sulfate liposome injection using ultra-high performance liquid chromatography tandem mass spectrometry.

Fen Yang, Hongyun Wang, Ming Liu, Pei Hu, Ji Jiang

Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences, Beijing 100730, China.

Journal of chromatography. A 2013 Feb 1

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Vincristine sulfate liposome is a liposomal formulation of vincristine sulfate, a traditional anticancer drug, encapsulated in the aqueous core of phospholipid/cholesterol liposomes, which are kinds of targeted carriers to enhance malignancy targeting, exposure and anticancer activity of the drug. To evaluate and compare the pharmacokinetics of nonliposomal and liposome-encapsulated VCR and pharmacodynamic relationships associated with the toxicity and the efficacy behavior, it is essential to have a reliable method of separating the free and liposomal forms of the drug. In this paper, we have developed and validated methods to quantify the free vincristine (F-VCR) and total vincristine (T-VCR) in human plasma after intravenous administration of vincristine sulfate liposome injection (VSLI). The methods involve solid-phase extraction (SPE) for separating the F-VCR and liquid-liquid extraction (LLE) for releasing the VCR totally from the liposomal forms followed by an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). The methods were validated over the concentration range of 0.2-50 ng/mL for F-VCR and 0.5-400 ng/mL for T-VCR, respectively. Inter- and intra-day precision (RSD%) were ≤4.7% for F-VCR and ≤9.8% for T-VCR, respectively. The accuracies were between -2.3 and 9.1% for F-VCR and between -3.2 and 6.9% for T-VCR, respectively. The extraction recovery and the matrix effect were investigated. The methods were successfully applied to the pharmacokinetic study of VSLI in Chinese subjects with lymphoma. Copyright © 2012 Elsevier B.V. All rights reserved.

Citation

Fen Yang, Hongyun Wang, Ming Liu, Pei Hu, Ji Jiang. Determination of free and total vincristine in human plasma after intravenous administration of vincristine sulfate liposome injection using ultra-high performance liquid chromatography tandem mass spectrometry. Journal of chromatography. A. 2013 Feb 1;1275:61-9