Liquid chromatographic-tandem mass spectrometric method for the simultaneous quantitation of telmisartan and hydrochlorothiazide in human plasma.
A rapid and sensitive method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the simultaneous determination of telmisartan and hydrochlorothiazide in human plasma. Sample preparation involved liquid-liquid extraction with diethyl ether-dichloromethane (60:40, v/v). The analytes and internal standard, probenecid, were separated on a Venusil XBP-C(8) column using gradient elution with acetonitrile-10 mM ammonium acetate-formic acid at a flow rate of 1.2 mL/min. Detection was by electrospray negative ionization mass spectrometry using multiple reaction monitoring of the transitions at m/z 513.0-->469.4 for telmisartan, m/z 295.9-->268.9 for hydrochlorothiazide and m/z 283.9-->239.9 for probenecid. For both analytes, the method was linear in the range 1.00-600 ng/mL with intra- and inter-day precision (as relative standard deviation) <or=10.6% and accuracy (as relative error) <or=4.2%. The assay was successfully applied to a pharmacokinetic study in 9 healthy volunteers given a single oral dose of a combination tablet containing telmisartan 80 mg and hydrochlorothiazide 12.5 mg.
Yan
Tingting
T
Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun 130021, PR China.
Li
Hao
H
Deng
Lili
L
Guo
Yingjie
Y
Yu
Weisong
W
Fawcett
J Paul
JP
Zhang
Dan
D
Cui
Yimin
Y
Gu
Jingkai
J
D047228:Angiotensin II Type 1 Receptor Blockers / Q000097:blood* / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D001565:Benzoates / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004232:Diuretics / Q000097:blood* / Q000493:pharmacokinetics; D004338:Drug Combinations; D004355:Drug Stability; D017408:Guidelines as Topic; D006801:Humans; D006852:Hydrochlorothiazide / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015394:Molecular Structure; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000077333:Telmisartan; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D004232:Diuretics; D004338:Drug Combinations; D013607:Tablets; D006852:Hydrochlorothiazide; D000077333:Telmisartan