title: High-Throughput HPLC-MS/MS Method for Quantification of Ibuprofen Enantiomers in Human Plasma: Focus on Investigation of Metabolite Interference.
abstract: In this research, as a part of the development of fast and reliable HPLC-MS/MS method for quantification of ibuprofen (IBP) enantiomers in human plasma, the possibility of IBP acylglucoronide (IBP-Glu) back-conversion was assessed. This involved investigation of in source and in vitro back-conversion. The separation of IBP enantiomers, its metabolite and rac-IBP-d3 (internal standard), was achieved within 6 min using Chiracel OJ-RH chromatographic column (150 × 2.1 mm, 5 μm). The followed selected reaction monitoring transitions for IBP-Glu (m/z 381.4 → 205.4, m/z 381.4 → 161.4 and m/z 205.4 → 161.4) implied that under the optimized electrospray ionization parameters, in source back-conversion of IBP-Glu was insignificant. The results obtained after liquid-liquid extraction of plasma samples spiked with IBP-Glu revealed that the amount of IBP enantiomers generated by IBP-Glu back-conversion was far <20% of lower limit of quantification sample. These results indicate that the presence of IBP-Glu in real samples will not affect the quantification of the IBP enantiomers; thereby reliability of the method was improved. Additional advantage of the method is the short analysis time making it suitable for the large number of samples. The method was fully validated according to the EMA guideline and was shown to meet all requirements to be applied in a pharmacokinetic study.
authors.affiliation: Institute of Applied Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy, University of Ss. Cyril and Methodius, 1000 Skopje, Macedonia natalijan@ff.ukim.edu.mk n.cukic@yahoo.com.
authors.forename: Natalija
authors.initials: N
authors.lastname: Nakov
authors.affiliation: Institute of Applied Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy, University of Ss. Cyril and Methodius, 1000 Skopje, Macedonia.
authors.forename: Liljana
authors.initials: L
authors.lastname: Bogdanovska
authors.affiliation: Institute of Applied Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy, University of Ss. Cyril and Methodius, 1000 Skopje, Macedonia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Acevska
authors.affiliation: Institute of Applied Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy, University of Ss. Cyril and Methodius, 1000 Skopje, Macedonia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Tonic-Ribarska
authors.affiliation: Institute of Applied Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy, University of Ss. Cyril and Methodius, 1000 Skopje, Macedonia.
authors.forename: Rumenka
authors.initials: R
authors.lastname: Petkovska
authors.affiliation: Institute of Applied Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy, University of Ss. Cyril and Methodius, 1000 Skopje, Macedonia.
authors.forename: Aneta
authors.initials: A
authors.lastname: Dimitrovska
authors.affiliation: Alexander University Hospital, Faculty of Medicine, Medical University of Sofia, 1431 Sofia, Bulgaria.
authors.forename: Lilia
authors.initials: L
authors.lastname: Kasabova
authors.affiliation: Alexander University Hospital, Faculty of Medicine, Medical University of Sofia, 1431 Sofia, Bulgaria.
authors.forename: Dobrin
authors.initials: D
authors.lastname: Svinarov
mesh_terms: D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007052:Ibuprofen / Q000032:analysis / Q000097:blood*; D015203:Reproducibility of Results; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D007052:Ibuprofen