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

► An assay for the determination of free and total vincristine (VCR) in plasma. ► The first validated method of separating free VCR from liposomes. ► The SPE method was feasible to separate free VCR without liposomal damage. ► The present method was validated according to FDA guidance. ► The method...

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Bibliographic Details
Published in:Journal of Chromatography A Vol. 1275; pp. 61 - 69
Main Authors: Yang, Fen, Wang, Hongyun, Liu, Ming, Hu, Pei, Jiang, Ji
Format: Journal Article
Language:English
Published: Amsterdam Elsevier B.V 01.02.2013
Elsevier
Subjects:
Analysis
anticarcinogenic activity
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - blood
Biological and medical sciences
cholesterol
Chromatography, High Pressure Liquid - methods
Drug Stability
Free vincristine
General pharmacology
Humans
intravenous injection
ionization
Linear Models
Liposomes - administration & dosage
Liposomes - blood
Liquid-Liquid Extraction
Lymphoma
Lymphoma - blood
Lymphoma - drug therapy
Medical sciences
monitoring
pharmacokinetics
Pharmacology. Drug treatments
phospholipids
Reproducibility of Results
Sensitivity and Specificity
Solid Phase Extraction
SPE
Spectrometry, Mass, Electrospray Ionization
tandem mass spectrometry
Tandem Mass Spectrometry - methods
UHPLC–MS/MS
ultra-performance liquid chromatography
vincristine
Vincristine - administration & dosage
Vincristine - blood
Vincristine - pharmacokinetics
Vincristine sulfate liposomes
Vincristine sulfate liposomes
UHPLC–MS/MS
SPE
Lymphoma
Free vincristine
Antineoplastic agent
Encapsulation
Ultra performance liquid chromatography
Solid phase extraction
Biological fluid
Tandem mass spectrometry
Chemical analysis
Intravenous administration
Free form
Solvent extraction
Electrospray
Blood
Chemical enrichment
Blood plasma
Alkaloid
Sample preparation
Lymphoproliferative syndrome
Antimitotic
Quantitative analysis
Trace analysis
Human
Validation
Liquid liquid extraction
Coupled method
Liposome
Patient
Malignant hemopathy
Vincristine
UHPLC-MS/MS
Pharmacokinetics
Cancer
ISSN:0021-9673, 1873-3778, 1873-3778
Online Access:Get full text
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Summary:► An assay for the determination of free and total vincristine (VCR) in plasma. ► The first validated method of separating free VCR from liposomes. ► The SPE method was feasible to separate free VCR without liposomal damage. ► The present method was validated according to FDA guidance. ► The method was applied to the PK studies of liposomal VCR in subjects with lymphoma. 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 0.2–50ng/mL for F-VCR and 0.5–400ng/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.
Bibliography:http://dx.doi.org/10.1016/j.chroma.2012.12.026
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content type line 23
ISSN:0021-9673
1873-3778
1873-3778
DOI:10.1016/j.chroma.2012.12.026