Abstract

VALIDATED UPLC/Q-TOF-MS METHOD FOR SIMULTANEOUS DETERMINATION OF ANTI-HYPERTENSIVE AND DIURETIC DRUGS IN HUMAN PLASMA AND ITS APPLICATION TO PHARMACOKINETIC STUDY

Hamid Khan*

ABSTRACT

In the presented work the ultra-performance liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC/Q-TOF-MS) method has been developed for simultaneous determination of telmisartan, hydrochlorothiazide and its major metabolite chlorothiazide in human plasma. For identification of drugs, the Q-TOF mass spectrometer was operated in negative ionization mode and quantification was done using the MS/MS transitions at m/z 513.18 to 469.13 for telmisartan, 295.80 to 204.94 for hydrochlorothiazide and 268.80 to 169.98 for chlorothiazide. The chromatographic separation was achieved on Acquity UPLCTM BEH C18 (100.0 × 2.1 mm, 1.7μm) column using isocratic mobile phase consisting of acetonitrile-2mM ammonium acetate (50:50, v/v) at a flow rate of 0.25 mL/min. The elution of telmisartan, hydrochlorothiazide and chlorothiazide was occurred at 2.25, 1.22, 1.50 min, respectively. The calibration curves were linear over the concentration range of 1-1000 ng/mL for all the compounds. The developed method was validated according to ICH guidelines. The method was applied for pharmacokinetic study of telmisartan and hydrochlorothiazide in human plasma.

Keywords: UPLC/Q-TOF-MS, Telmisartan, Hydrochlorothiazide, Chlorothiazide, Pharmacokinetic Study.