Rapid and sensitive determination of indapamide in human blood by liquid chromatography with electrospray ionization mass spectrometric detection: application to a bioequivalence study
Tang, J.; Li, J.; Sun, J.; Yin, J.; He, Z.
Die Pharmazie 60(11): 819-822
2005
ISSN/ISBN: 0031-7144 PMID: 16320942 Document Number: 584894
A rapid and sensitive method using liquid chromatography with electrospray ionization mass spectrometric detection was developed and validated for the determination of indapamide in human blood. Blood samples were extracted with n-hexane-dichloromethane (1 : 1, v/v) and separation was performed on a Symmetry C-18 column (150 x 3.9 mm i.d., 5 mu m) with the mobile phase consisting of acetonitrile-water (60 : 40, v/v). Indapamide and internal standard (propylparaben) were detected by negative electrospray ionization and selected ion recording (SIR) at m/z 364 for indapamide and m/z 179 for propylparaben. This method has a lower limit of quantification (LLOQ) 2.0 mu g/L with a linear calibration range of 2.0 mu g/L to 120 mu g/L. The method showed excellent reproducibility with an inter- and intra-assay precision of <9.4% (% RSD), as well as excellent accuracy with an inter- and intra-assay accuracy of between 98.0 and 102%. Furthermore, the method was successfully applied to a bioequivalence study in which 20 healthy volunteers received a single oral dose of 3 mg reference and test sustained-release indapamide formulations, in an open, two-period, randomized crossover protocol. The maximum blood concentrations (C-max) were 60.3 +/- 22.6 mu g/L and 57.6 +/- 18.7 mu g/L at 13.1 +/- 6.9 h and 18.3 +/- 7.4 h, the times to reach the peak concentration (T-max), for the test and reference tablets, respectively. The relative bioavailability of the test tablets was 110.1 +/- 34.5%, compared with the reference tablets. There were no statistically significant differences in the main pharmacokinetic parameters, and the two formulations were judged to be bioequivalent.