title: 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.
abstract: 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.
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Yang
authors.forename: Hongyun
authors.initials: H
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D008081:Liposomes / Q000008:administration & dosage / Q000097:blood*; D059625:Liquid-Liquid Extraction; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014750:Vincristine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D014750:Vincristine