title: Enantioselective LC/MS method for the determination of an antimalarial agent Fenozan B07 in dog plasma.
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.
authors.affiliation: Department of Pharmacokinetics and Analytical Chemistry, Centro de Investigación y Desarrollo Aplicado, S.A.L., Barcelona, Spain. c.maraschiello@cidasal.com
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Maraschiello
authors.forename: Jaume
authors.initials: J
authors.lastname: Vilageliu
authors.forename: Isabel
authors.initials: I
authors.lastname: Dorronsoro
authors.forename: Ana
authors.initials: A
authors.lastname: Martinez
authors.forename: Pablo
authors.initials: P
authors.lastname: Floriano
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gómez-Acebo
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000097:blood* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D004355:Drug Stability; D005615:Freezing; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D010545:Peroxides / Q000097:blood* / Q000737:chemistry; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013141:Spiro Compounds / Q000097:blood* / Q000737:chemistry; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D000962:Antimalarials; D010545:Peroxides; D013141:Spiro Compounds; C097757:Fenozan 50F