Abstract
A new, simple, sensitive, selective, rapid, and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for simultaneous quantification of Olmesartan and hydrochlorothiazide in human plasma. Simple liquid–liquid extraction procedure was applied for plasma sample pretreatment using a mixture of diethyl ether and dichloromethane, as an extraction solution. Analytes were separated on UNISOL C18 150*4.6 mm, 5 µm column using methanol, and 2 mM ammonium acetate pH 5.5 (80:20, v/v) as a mobile phase and detected by electrospray ionization in the multiple reaction monitoring (MRM) mode. The mass transition ion pairs were followed in negative ion mode as m/z 445.20 → 148.90 for Olmesartan; m/z 451.40 → 154.30 for Olmesartan D6 and m/z 295.80 → 205.10 for hydrochlorothiazide; m/z 298.90 → 206.30 for hydrochlorothiazide 13C D2. The method showed excellent linearity (r 2 > 0.99) over the concentration range of 5.002–2,599.934 ng/ml for Olmesartan and from 3.005 to 499.994 ng/ml for hydrochlorothiazide. Precision (% CV) and accuracy (% bias) for Olmesartan were found in the range of 3.07–9.02% and −5.00–0.00%, respectively. Precision (% CV) and accuracy (% bias) for hydrochlorothiazide were found in the range of 3.32–8.21% and 1.99–3.80%, respectively. This as developed novel and high-throughput liquid–liquid extraction bioanalytical method has substantial innovative value with the benefits of cost effectiveness, good extraction efficiency, shorter analysis run time, low organic solvent consumption, and simpler procedure over the previously reported solid-phase extraction method. The application of this method in pharmacokinetic studies was further demonstrated successfully through a bioequivalence study conducted on healthy human subjects, following oral administration of combined formulation of Olmesartan medoxomil and hydrochlorothiazide in fixed-dose tablet.
Highlights
Hypertension or high blood pressure, sometimes called arterial hypertension, is a chronic medical condition in which the blood pressure in the arteries is elevated due to the higher force exerted by blood against the wall of the blood vessels (Mancia et al, 2013)
Since OLM D6 and HCTZ 13C D2 differ from their respective analytes only in terms of having different isotopic atoms, they were expected to display nearly similar chromatographic behavior
Limitations exist in the conventional methods based on spectrophotometer, HPLC, and HPTLC, which were used for the quantification of drugs
Summary
Hypertension or high blood pressure, sometimes called arterial hypertension, is a chronic medical condition in which the blood pressure in the arteries is elevated due to the higher force exerted by blood against the wall of the blood vessels (Mancia et al, 2013). 1.13 billion people or ~26% of the adult population of the world were reported with hypertension as per the report of World Health Organization (WHO). Olmesartan medoxomil and hydrochlorothiazide are reported as the two most preferred drugs of choice for combination therapy of hypertension (Chrysant et al, 2004; Greathouse, 2006; Bramlage et al, 2013). Olmesartan medoxomil has the better antihypertensive effect when treatment is combined with diuretics (Zhang et al, 2017) and is described chemically as the (5‐methyl‐2‐oxo‐1,3‐dioxol‐4‐yl) methyl ester of 4‐(1‐ hydroxy‐1‐methylethyl)‐2‐propyl‐1‐{[20‐(1H‐tetrazol‐5‐yl) [1,10‐biphenyl]‐4‐yl]methyl}‐1H‐imidazole‐5‐carboxylic acid. Low plasma rennin activity is often associated with hypertension, and HCTZ is reported to be effective for treatment of individuals with low rennin hypertension and may require a longer treatment regime (Goswami et al, 2008). For proper management of hypertension, it is recommended to provide a combination therapy of HCTZ along with an antihypertensive drug (Zanchetti, 2003)
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