Determination of Candesartan and Hydrochlorothiazide in Human Plasma by HPLC Coupled with Mass Spectrometry

Abstract

Quantitative determination of hydrochlorothiazide (HCTZ) and candesartan (CDS) in human plasma in volunteers was performed using a sensitive, selective and specific LC-MS method which has been developed and validated before the study. The study was performed by means of a liquid chromatograph Shimadzu Prominence equipped with a mass spectrometer LCMS-2020. Analytical column PerfectBond ODS-HD HPLC-column 5 µm 250 × 3.0 mm with a pre-column cartridge PerfectBond ODS-HD 5 µm 10 × 3.0 mm, double source of ionization for LCMS-2020 (electrospray (ESI) and chemical (APCI)) and software LabSol LCMS V5 LCMS2020 systempack were used. The low limit of the quantitative determination for HCTZ and CDS made up 10 ng/ml. m/z for CDS 441.20-positive scan, m/z for HCTZ 295.90-negative scan. The method has been applied to a pharmacokinetic study of 12.5 mg HCTZ and 16 mg CDS tablet in healthy volunteers.

LC–MS/MS Method for Quantitation of Hydrochlorothia-zide and Nifedipine in Human Plasma

“…The mean extraction recoveries of analytes from human plasma were 98.6 ± 0.6% (HCTZ), 97.4 ± 3.1% (NFP) and 89.8 ± 2.4% for the IS (Table 3). The recoveries reported in this method were significantly higher than those in previously reported publications (Ramakrishna N. et al, 2005;Shah H. et al, 2009;Olga S. et al, 2014;Xiangjun et al, 2014;Ramkumar et al, 2015;Jaivik V. et al, 2017) for HCTZ and (Wang et al, 2011;Hisham S. et al, 2000;Yunzhen G. et al, 2007;Essam E. et al, 2014) for NFP. This method yielded higher recoveries with better reproducibility due to the use of 1.5mL polypropylene tubes in sample processing compared to other reported methods that used larger tubes (15mL) hence loss of drugs along the walls of the tubes.…”

“…These unfavorable pharmacokinetics and physical characteristic make the determination of nifedipine in plasma tricky. Several methods have been reported for quantification of HCTZ and NFP individually (Ramakrishna N. et al, 2005;Wang et al, 2011;Shah H. et al, 2009;Hisham S et al, 2000;Yunzhen G. et al, 2007), or simultaneously with other antihypertensive agents (Olga S. et al, 2014;Xiangjun et al, 2014;Ramkumar et al, 2014;Jaivik V. et al, 2017;Essam E et al, 2014) in human plasma. Hisham S. et al, 2000; developed a method for quantitation of nifedipine in human plasma, the LC-UV method was limited in quantifying lower levels of the drug in a biological matrix due to its low sensitivity and poor selectivity.…”

Simultaneous determination of candesartan and hydrochlorothiazide in human plasma by LC-MS/MS

“…Thorough survey of literature disclosed good number of analytical methods which include UV (Erk, 2003a;Naseemet al, 2009), HPTLC (Bipin, Sachinet al, 2008), HPLC (Qutab et al, 2007;Be et al, 1990;Richter, Oertel, Kir, 1996;Erk, 2003b;Zendelovska, Stafilovm Molisevski, 2004;Balamuralikrishna, Syamasundar, 2010;Annapurna, Narendra, Ravi, 2012;Veeranjaneyulu, Aneesha, Nandakishore, 2012;Narendra, Satyanarayana, Ganga, 2012), LC-MS (Brushinina et al, 2014;Surbhi et al, 2010;Bharathi et al, 2012) and UPLC-MS (Singh et al, 2014) methods are available for the evaluation of CAN and HCT in bulk, pharmaceutical dosage forms and in biological samples individually or in combination with other drugs. To our knowledge, no LC-MS/MS method is available for the simultaneous evaluation of these drugs in human plasma using isotopic internal standards.…”