title: Determination of levocetirizine in human plasma by liquid chromatography-electrospray tandem mass spectrometry: application to a bioequivalence study.
abstract: We describe a liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for levocetirizine quantification (I) in human plasma. Sample preparation was made using a fexofenadine (II) addition as internal standard (IS), liquid-liquid extraction using cold dichloromethane, and dissolving the final extract in acetonitrile. I and II (IS) were injected in a C18 column and the mobile phase composed of acetonitrile:water:formic acid (80.00:19.90:0.10, v/v/v) and monitored using positive electrospray source with tandem mass spectrometry analyses. The selected reaction monitoring (SRM) was set using precursor ion and product ion combinations of m/z 389>201 for I and m/z 502>467 for II. The limit of quantification and the dynamic range achieved were 0.5ng/mL and 0.5-500.0ng/mL. Validation results on linearity, specificity, accuracy, precision and stability, as well as its application to the analysis of plasma samples taken up to 48h after oral administration of 5mg of levocetirizine dichloridrate in healthy volunteers demonstrate its applicability to bioavailability studies.
authors.affiliation: Core Clinical Research, 12914-160 Bragança Paulista, SP, Brazil. mrmorita1@yahoo.com.br
authors.forename: M R
authors.initials: MR
authors.lastname: Morita
authors.forename: D
authors.initials: D
authors.lastname: Berton
authors.forename: R
authors.initials: R
authors.lastname: Boldin
authors.forename: F A P
authors.initials: FA
authors.lastname: Barros
authors.forename: E C
authors.initials: EC
authors.lastname: Meurer
authors.forename: A R
authors.initials: AR
authors.lastname: Amarante
authors.forename: D R
authors.initials: DR
authors.lastname: Campos
authors.forename: S A
authors.initials: SA
authors.lastname: Calafatti
authors.forename: R
authors.initials: R
authors.lastname: Pereira
authors.forename: E
authors.initials: E
authors.lastname: Abib
authors.forename: J
authors.initials: J
authors.lastname: Pedrazolli
mesh_terms: D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D017332:Cetirizine / Q000097:blood* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D006634:Histamine H1 Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008875:Middle Aged; D010879:Piperazines / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013810:Therapeutic Equivalency
chemical_list: D006634:Histamine H1 Antagonists; D010879:Piperazines; C472067:levocetirizine; D017332:Cetirizine