Simultaneous determination of hydrochlorothiazide, quinapril and quinaprilat in human plasma by liquid chromatography-tandem mass spectrometry

J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Sep 15;873(1):59-69. doi: 10.1016/j.jchromb.2008.07.046. Epub 2008 Aug 7.


A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous estimation of hydrochlorothiazide, quinapril and its metabolite quinaprilat in human plasma. After solid phase extraction (SPE), the analytes and IS were chromatographed on a hypurity C8 (100 mm x 2.1 mm i.d., 5 microm particle size) column using 2 microL injection volume with a run time of 2.8 min. An isocratic mobile phase consisting of 0.5% (v/v) formic acid:acetonitrile (25:75, v/v) was used to separate all these drugs. The precursor and product ions of these drugs were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring mode (MRM) without polarity switch. The proposed method was validated over the range of 5-500 ng/mL for hydrochlorothiazide method and 5-1500 ng/mL for quinapril and quinaprilat. Inter-batch and intra-batch precision (coefficient of variation - % CV) across five validation runs lower limit of quantitation (LLOQ), lower quality control (LQC), middle quality control (MQC), higher quality control (HQC) and upper limit of quantitation (ULOQ) was less than 15. The accuracy determined at these levels was within +/-13% in terms of relative percentage error.

MeSH terms

  • Chromatography, High Pressure Liquid / methods*
  • Humans
  • Hydrochlorothiazide / blood*
  • Hydrochlorothiazide / pharmacokinetics
  • Quinapril
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods*
  • Tetrahydroisoquinolines / blood*
  • Tetrahydroisoquinolines / pharmacokinetics
  • Therapeutic Equivalency


  • Tetrahydroisoquinolines
  • Hydrochlorothiazide
  • quinaprilat
  • Quinapril