Hydrochlorothiazide/Valsartan

Various groups of antihypertensive drugs targeting different pathways have been developed; however, the pharmacometabolic responses to these drugs have rarely been compared to elucidate the common pathway of blood pressure regulation. Here, we performed a comparative multi-dimensional pharmacometabolic study on the four major lines of antihypertensive drugs, namely angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics (DIURs), through ultra-performance liquid chromatography coupled to quantum time-of-flight mass spectrometry. Two hundred fifty patients with young-onset hypertension, who were equally divided among five study groups: non-medicated, ACEi, ARB, CCB, and DIUR groups, were recruited. In a metabolome-wide association study conducted through analysis of covariance, 37 molecular features significantly associated with pharmacometabolic responses to antihypertensive drugs were identified. One-third of these features were shared by multiple medications. ACEis, ARBs, and DIURs shared more features than CCB, partially reflecting that ACEis, ARBs, and DIURs affect the renin-angiotensin-aldosterone system. Thirteen molecular features were consistently identified by all four models of the analysis of covariance. A tandem mass spectrometry (or MS/MS) experiment was performed to decipher the chemical structure of these 13 molecular features, including ARB-associated lysophosphatidylcholine (P4135), CCB-associated diacylglycerol(15:0/18:2) (P1175), and DIUR-associated oleamide (P1516). In addition, diacylglycerol(15:0/14:2) (P408) was significantly associated with the pharmacometabolic response to all four antihypertensive drugs. The identified metabolites provide insights into the mechanisms of blood pressure regulation and potential predictive markers of pharmacometabolic responses to antihypertensive drugs.

A selective, accurate, precise, and highly sensitive HPTLC assay with reflectance/fluorescence densitometry was developed to separate and quantify some angiotensin II receptor blockers (ARBs), namely, losartan potassium, irbesartan, valsartan, and olmesartan medoxomil, in tablets and plasma. Separation of the target ARBs was performed on precoated silica gel HPTLC plates developed using chloroform–glacial acetic acid (7.5 + 2.5, v/v) mobile phase. The drugs were adequately resolved. After the exposure of the chromatograms to concentrated hydrochloric acid vapor for 10 min, the scanner was set in the reflectance/fluorescence mode with 255 nm excitation wavelength and >400 nm emission filter. The linear regression analysis data for the calibration curves of all studied drugs produced a good linear relationshipwith correlation coefficients ranging from 0.9991 to0.9999 over the concentration range of 2–20 ng/band. LOD and LOQ values of all studied drugs ranged from 0.6 to 0.8 and from 1.7 to 2.4 ng/band, respectively. The developed method was successfully applied for analysis of the target ARBs in tablets and spiked human plasma samples with good precision and accuracy.