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J Pharm Biomed Anal. 2019 Jul 15;171:111-117. doi: 10.1016/j.jpba.2019.03.048. Epub 2019 Mar 26.

Development and validation of a simple, fast, and sensitive LC/MS/MS method for the quantification of oxfendazole in human plasma and its application to clinical pharmacokinetic study.

Author information

1
Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, IA, 52242, USA.
2
College of Pharmacy, University of Iowa, IA, 52242, USA.
3
Department of Internal Medicine, College of Medicine, University of Iowa, IA, 52242, USA.
4
Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, IA, 52242, USA. Electronic address: guohua-an@uiowa.edu.

Abstract

The most popular standard treatments for soil transmitted helminths in humans including mebendazole, albendazole, levamisole, and pyrantel pamoate, show greatly variable efficacy against different species of parasites and have unfavorable pharmacokinetic characteristics, such as short half-life. The transition of oxfendazole, a potent broad-spectrum anthelmintic with long half-life, from veterinary medicine to human use has been considered as a promising approach. However, analytical methods for the quantitative detection of oxfendazole in human matrix are very limited and lack sensitivity. In this study, we have developed a high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the quantification of oxfendazole in human plasma using albendazole as an internal standard. The established method was fully validated with lower limit of quantitation (LLOQ) of 0.5 ng/mL and linearity in the range of 0.5-1000 ng/mL; intra-day and inter-day accuracies ranged from 2.6 to 9.5% for 3 quality control levels (1.5 ng/mL, 75 ng/mL, and 750 ng/mL) and LLOQ; intra-day and inter-day precision was ≤13.6% for quality controls and ≤15.1% for LLOQ; matrix factor and extraction recovery were consistent with coefficient of variation of less than 15.0%. Other parameters including matrix selectivity, injection carryover, reinjection reproducibility, hemolysis effect, interference of analyte with internal standard, dilution integrity, freeze/thaw stability, whole blood stability, and stock solution stability were also validated and met the acceptance criteria. The assay was successfully applied to quantify oxfendazole plasma concentration in healthy adult volunteers after the administration of multiple oral doses of oxfendazole.

KEYWORDS:

Clinical trial; Human plasma; LC/MS/MS; Oxfendazole; Protein precipitation; Validation

PMID:
30981954
PMCID:
PMC6545882
[Available on 2020-07-15]
DOI:
10.1016/j.jpba.2019.03.048
[Indexed for MEDLINE]

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