Abstract
•Novel RP-HPLC method for simultaneous estimation of two antihypertensive combinations along with drug degradates and process impurities.•Separation and quantitation with high sensitivity, short analysis time, and minimum sample pretreatment steps.•The developed method will decrease time and money required for analysis of each binary mixture alone. The method can be applied for studying the impurity profile of the studied drugs.
Hydrochlorothiazide is a widely used thiazide diuretic. Its combinations with either olmesartan medoxomil or fosinopril sodium are well known antihypertensive combinations that compare positively than other related combined therapies. A first RP-HPLC method was introduced for simultaneous estimation of two antihypertensive combinations containing hydrochlorothiazide with either olmesartan medoxomil or fosinopril sodium. The work was extended to quantify the drugs along with their degradation products; salamide as hydrochlorothiazide degradate and olmesartan as olmesartan medoxomil degradate. Also, it succeeded to determine the pharmacopoeial impurity of hydrochlorothiazide (chlorothiazide). The established RP-HPLC was performed on RP-C18 column utilizing gradient mixture of 0.05 M KH2PO4 (pH 3 with aqueous O-phosphoric acid), acetonitrile, and methanol. Temperature was adjusted to 35 °C and UV detection was done at 205 nm for fosinopril sodium and at 225 nm for the rest of the cited components.
ICH guidelines were used to validate the method and all the results affirmed efficiency of the method. In addition, it was effectively used for measuring hydrochlorothiazide in binary mixtures with either olmesartan medoxomil or fosinopril sodium in their available pharmaceutical formulation. Also, the statistical comparison with published methods was executed and no noteworthy difference concerning accuracy and precision was detected.