Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma using HPLC coupled with tandem mass spectrometry: Application to bioequivalence studies.
A sensitive, specific and selective liquid chromatography/tandem mass spectrometric method has been developed and validated for the simultaneous determination of irbesartan and hydrochlorothiazide in human plasma. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard losartan were separated on a reverse phase C(18) column (50mmx4mm, 3microm) using water with 2.5% formic acid, methanol and acetonitrile (40:45:15, v/v/v (%)) as a mobile phase (flow rate of 0.70mL/min). Irbesartan and hydrochlorothiazide were ionized using ESI source in negative ion mode, prior to detection by multiple reaction monitoring (MRM) mode while monitoring at the following transitions: m/z 296-->269 and m/z 296-->205 for hydrochlorothiazide, 427-->175 for irbesartan. Linearity was demonstrated over the concentration range 0.06-6.00microg/mL for irbesartan and 1.00-112.00ng/mL for hydrochlorothiazide. The developed and validated method was successfully applied to a bioequivalence study of irbesartan (300mg) with hydrochlorothiazide (12.5mg) tablet in healthy volunteers (N=36).
Tutunji
Lara F
LF
Faculty of Pharmacy, University of Jordan, Amman, Jordan. l.tutunji@ju.edu.jo
Tutunji
Maha F
MF
Alzoubi
Mamoun I
MI
Khabbas
Manal H
MH
Arida
Adi I
AI
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D004338:Drug Combinations; D004355:Drug Stability; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000592:standards; D013777:Tetrazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency; D055815:Young Adult
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D004232:Diuretics; D004338:Drug Combinations; D013607:Tablets; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000077405:Irbesartan