Liquid chromatography–mass spectrometry analysis of diethylcarbamazine in human plasma for clinical pharmacokinetic studies

•First reported LC–MS method for diethylcarbamazine (DEC) in plasma.•A stable isotope-labeled internal standard is used.•Method has lower quantitation limits and requires less plasma than previous methods.•Precise and accurate DEC assay suitable for clinical pharmacokinetic studies.•Methodology allo...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2014-09, Vol.98, p.307-310
Main Authors: Schmidt, Mark S., King, Christopher L., Thomsen, Edward K., Siba, Peter M., Sanuku, Nelly, Fleckenstein, Lawrence
Format: Article
Language:English
Subjects:
Albendazole - blood
Albendazole - chemistry
Antifilarial
Chromatography, Liquid - methods
Diethylcarbamazine
Diethylcarbamazine - blood
Diethylcarbamazine - chemistry
Elephantiasis, Filarial - blood
Humans
Ivermectin - blood
Ivermectin - chemistry
Liquid chromatography–mass spectrometry
Mass Spectrometry - methods
Plasma
Plasma - chemistry
Solid Phase Extraction - methods
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Summary:•First reported LC–MS method for diethylcarbamazine (DEC) in plasma.•A stable isotope-labeled internal standard is used.•Method has lower quantitation limits and requires less plasma than previous methods.•Precise and accurate DEC assay suitable for clinical pharmacokinetic studies.•Methodology allows broader range of laboratories to perform pharmacokinetic studies. A sensitive and selective liquid chromatographic method using mass spectrometric detection was developed for the determination of diethylcarbamazine (DEC) in human plasma. DEC and its stable isotope internal standard d3-DEC were extracted from 0.25mL of human plasma using solid phase extraction. Chromatography was performed using a Phenomenex Synergi 4μ Fusion-RP column (2mm×250mm) with gradient elution. The retention time was approximately 4.8min. The assay was linear from 4 to 2200ng/mL. Analysis of quality control samples at 12, 300, and 1700ng/mL (N=15) had interday coefficients of variation of 8.4%, 5.4%, and 6.2%, respectively (N=15). Interday bias results were −2.2%, 6.0%, and 0.8%, respectively. Recovery of DEC from plasma ranged from 84.2% to 90.1%. The method was successfully applied to clinical samples from patients with lymphatic filariasis from a drug–drug interaction study between DEC and albendazole and/or ivermectin.
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2014.05.016