Enantioselective LC/MS method for the determination of an antimalarial agent Fenozan B07 in dog plasma

Chirality
Ciriaco MaraschielloEduardo Gómez-Acebo

Abstract

A chiral liquid chromatography/mass spectrometry (LC/MS) bioanalytical procedure has been developed for the analysis of the antimalaric agent Fenozan B07 in dog plasma. Normal-phase chromatography involving a phenylcarbamate derivative of cellulose coated on silica gel as the chiral stationary phase was used to resolve (-)-(S,S)-B07 from (+)-(R,R)-B07. The enantiomers were detected by a mass spectrometer equipped with an atmospheric pressure chemical ionization (APCI) interface operated in the negative ion mode. A mass spectrum, characterized by a base peak of m/z 285, was obtained for each enantiomer. The m/z 285 ion was very specific for the analysis of both enantiomers in the plasma. The selected ion monitoring analysis of the plasma samples was therefore performed at m/z 285 for quantitative purposes. The enantiomers were extracted from the plasma in a basic medium and purified by solid-phase extraction using a hydrophilic-lipophilic balanced sorbent. A lower limit of quantification of 2 ng/mL in plasma was achieved for both enantiomers. The quantitative procedure reported in this study was highly specific and sensitive, and was validated according to the FDA guidance on bioanalytical method validation.

References

Jun 4, 1999·Trends in Pharmacological Sciences·M A van AgtmaelC J van Boxtel
May 4, 1998·Angewandte Chemie·Yoshio Okamoto, Eiji Yashima

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Citations

Jan 31, 2007·Journal of Mass Spectrometry : JMS

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