A highly sensitive bioanalytical method for the quantification of vinblastine, vincristine, vinorelbine and 4-O-deacetylvinorelbine in human plasma using LC-MS/MS
van der Heijden, L T; Gebretensae, A; Thijssen, B; van Andel, L; Nijstad, A L; Wang, Y; Rosing, H; Huitema, A D R; Beijnen, J H
(2022) Journal of Pharmaceutical and Biomedical Analysis, volume 215, pp. 1 - 8
(Article)
Abstract
A highly sensitive method was developed for the quantification of vinblastine, vincristine, vinorelbine, and its active metabolite 4-O-deacetylvinorelbine in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Deuterated isotopes were used as internal standard and liquid-liquid extraction with tert-butyl methyl ether (TBME) was used for sample pre-treatment. The final extract
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was injected on a C18 column (50 × 2.1 mm ID, 5 µm). Gradient elution was used in combination with Reversed Phase chromatography to elute the analytes and internal standards from the column in 5 min and the API4000 triple quadrupole MS detector was operating in the positive ion mode. The calibration model, accuracy and precision, selectivity and specificity, dilution integrity, carryover, matrix factor and recovery, and stability were evaluated over a concentration range from 0.025 to 10 ng/mL for vinblastine, vinorelbine, and 4-O-deacetylvinorelbine and from 0.1 to 40 ng/mL for vincristine. The intra- and inter-assay bias and precisions were within ± 12.4% and ≤ 10.6%, respectively. This method was successfully applied to study the pharmacokinetics of vincristine in paediatrics and vinorelbine and 4-O-deacetylvinorelbine using in vivo mouse models.
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Keywords: Animals, Child, Chromatography, Liquid/methods, Drug Stability, Humans, Mice, Reproducibility of Results, Tandem Mass Spectrometry/methods, Vinblastine/chemistry, Vincristine, Vinorelbine, Human plasma, LC-MS/MS, Vinca-alkaloids, Pharmacokinetics, Drug Discovery, Analytical Chemistry, Spectroscopy, Clinical Biochemistry, Pharmaceutical Science, Journal Article
ISSN: 0731-7085
Publisher: Elsevier
Note: Publisher Copyright: © 2022 Elsevier B.V.
(Peer reviewed)