title: Simultaneous determination of losartan and hydrochlorothiazide in human plasma by LC/MS/MS with electrospray ionization and its application to pharmacokinetics.
abstract: A method based on a simple liquid-liquid extraction (LLE) followed by high-performance liquid chromatography with negative ion electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) detection was developed for the simultaneous determination of losartan (LOS) and hydrochlorothiazide (HCTZ) in human plasma, using valsartan (VAL) and chlorthalidone (CHTD) as an internal standard, respectively. The acquisition was performed in multiple reactions monitoring (MRM) and the limit of quantification was 4 ng/mL for both LOS and HCTZ. The method was linear in the studied range (4-800 ng/mL for LOS and 4-500 ng/mL for HCTZ). The intra-assay precisions ranged from 2.6-11.9% for LOS and 1.4-8.2% for HCTZ, while the inter-assay precisions ranged from 1.0-8.0% for LOS and 2.5-7.7% for HCTZ. The intra-assay accuracies ranged from 91.3 to 107.6% for LOS and 91.5 to 105.8% for HCTZ, while the inter-assay accuracies ranged from 99.9 to 106.4% for LOS and 97.4 to 101.4% for HCTZ. The analytical method was applied to a bioequivalence study, in which 28 healthy adult volunteers (14 men) received single oral doses (100 mg LOS + 25 mg HCTZ) of reference and test formulations, in an open, two-period, balanced randomized, crossover protocol. Based on the 90% confidence interval of the individual ratios for Cmax and AUC0-inf, it was concluded that the test formulation is bioequivalent to the reference Hyzaar formulation with respect to the rate and extent of absorption of both LOS and HCTZ.
authors.affiliation: ChromAnalysis - MCM Análises Laboratoriais SA, São Paulo-SP, Brazil.
authors.forename: Myriam C
authors.initials: MC
authors.lastname: Salvadori
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Moreira
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Borges
authors.forename: Maristela H
authors.initials: MH
authors.lastname: Andraus
authors.forename: Cristina P
authors.initials: CP
authors.lastname: Azevedo
authors.forename: Ronilson A
authors.initials: RA
authors.lastname: Moreno
authors.forename: Ney C
authors.initials: NC
authors.lastname: Borges
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002752:Chlorthalidone / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D019808:Losartan / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013777:Tetrazoles / Q000097:blood / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency; D014633:Valine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D000068756:Valsartan
chemical_list: D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000068756:Valsartan; D014633:Valine; D019808:Losartan; D002752:Chlorthalidone