Analytical Methods for Determination of Certain Antihypertensive Drugs

Hypertension is a key risk factor for cardiovascular diseases. Currently, around a third of people with hypertension are undiagnosed, and of those diagnosed, around half are not taking antihypertensive medications. The World Health Organization (WHO) estimates that high blood pressure directly or indirectly causes deaths of at least nine million people globally every year. In this literature review, we will introduce all reported methods that have been developed for determination of certain antihypertensive drugs such as irbesartan, losartan, candesartan, atenolol, bisoprolol and hydrochlorothiazide in their pure form, combined form with other drugs, combined form with degradation products, and in biological samples. We also will shed the light on the most important combination of drugs that are used for treatment of hypertension.


Pharmacological Action
Irbesartan is an angiotensin II receptor blocker, it inhibits the renin-angiotensin system which is responsible for effects such as vasoconstriction, stimulation of synthesis and release of aldosterone, and renal reabsorption of sodium. After binding with receptor, it leads to multiple effects including vasodilation, reduction in the production and secretion of aldosterone and the resulting effect is a decreasing in blood pressure [2]. It is well absorbed, does not need biotransformation to be converted to an active metabolite to reduce blood pressure, and is used in decreasing blood and kidney lipid but it has no effect on liver lipid [3]. Irbesartan is found to be effective in decreasing blood pressure with lower side effects as comparator antihypertensive drugs from different classes, including atenolol, amlodipine, hydrochlorothiazide, and enalapril [4] and it can improve the function of kidney of db/ db mice so is used in treatment for diabetic nephropathy [5]. In addition, irbesartan protects heart in presence of renal failure

Official Method of Determination
Irbesartan was official in B.P. 2013 [1] where a potentiometric titration method with perchloric acid in anhydrous acetic acid medium was described.

Official Method of Determination
Losartan is an official in B.P. 2013 [1] where a potentiometric titration with perchloric acid in anhydrous-acetic acid medium is described.

Pharmacological Action
Candesartan is an angiotensin II receptor blocker type 1 and used in treatment of various disorders like hypertension, heart failure, myocardial infarction, and diabetic nephropathy [86].

Official Method of Determination
Candesartan is official in B.P. 2013 [1] where it is determined by a potentiometric titration with 0.1 M perchloric acid in anhydrousacetic acid medium.

Pharmacological Action
Atenolol is b-blocker [111] used for the treatment of hypertension without compelling indications [112].

Official Method of Determination
Atenolol is official in B.P. 2013 [1] which describes a potentiometric titration with perchloric acid in anhydrous-acetic acid medium.

Literature Review
Spectrophotometric Methods: Pawar, et al. [113] described UV spectrophotometric method for the determination of atenolol and indapamide in a binary mixture. In this method, the signals were measured at 225 nm and 240 nm, respectively after dissolving atenolol and indapamide in methanol. In addition, two methods were used for the determination of atenolol in combined tablet dosage form. The first method was based on absorbance ratio at 232 nm (iso-absorptive point) whereas, the second method was depending on the first order derivative spectroscopy using 214 nm (zero cross for atenolol) [114]. Atenolol and chlorthalidone were dissolved in methanol followed by further dilutions with methanol then absorbance maxima were found to be 225 nm and 284 nm, respectively [115]. Another UV spectrophotometric method was The colored complexes were formed between atenolol and DDQ, DNP and TNP, were measured at λ max 590 nm, 420 nm and 420 nm, respectively [118]. Kinetic spectrophotometric method for the determination of atenolol in bulk form and tablet was described.
The method was based on measuring the decrease in absorbance of cerium at λ 360 nm [119]. DDQ was utilized for determination of atenolol forming charge transfer complex with maximum absorbance at λ max 405 nm [120]. Zero crossing method was used for the simultaneous determination of atenolol in combined dosage form. The absorbance was measured at λ max 275 nm [121].
UV-spectrophotometric method was applied for the estimation of atenolol in its tablet dosage forms. The absorbance was measured at λ max 273.2 nm in ammonium acetate solution [122]. The marketed combination of atenolol and amlodipine besylate was dissolved in 0.1N HCl. The spectra of amlodipine and atenolol exhibited λ of 239 nm and 228 nm, respectively [123]. Second order UV derivative spectrophotometric method for the determination of atenolol was used for quantification at 245 nm [124]. Moreover, Kudige and   [135].
Diffuse reflectance spectroscopy was used for the determination of atenolol in pharmaceutical formulations. In this method, the drug reacted with p-chloranil producing a colored compound with maximum absorption at λ max 550 nm [136]. Iontophoresis method was used to raise transdermal permation of atenolol from films [137]. Prashanth, et al. [138]

Pharmacological Action
Bisoprolol is b-blocker and is used in treatment of hypertension and heart failure [141,142].

Official Method of Determination
Bisoprolol is official in B.P. 2013 [1] which describes a potentiometric titration with perchloric acid in anhydrous-acetic acid medium.

Literature Review
Spectrophotometric Methods: Spectrophotometric determination of bisoprolol fumarate and amlodipine besylate in 10% methanol was based on using simultaneous equation method that had been carried out at two wavelengths 222 nm and 365 nm, respectively [143]. Hydrotropy solubilization agents were used for simultaneous spectrophotometric determination of bisoprolol fumarate in tablets with maximum absorbance at wavelength 271nm [144]. The formation of an ion pair complex between bisoprolol and methyl orange in acid medium was used as spectrophotometric method for determination of bisoprolol.
The produced complex was measured at 427 nm [145]. Two spectrophotometric methods were used for the determination of

Pharmacological Action
Hydrochlorothiazide is a thiazide diuretic and is considered the

Official Method of Determination
Hydrochlorothiazide is official in B.P. 2013 [1] where it was determined by chromatographic system. Simultaneous equation, absorption ratio and first order derivative spectroscopy methods had been used for spectrophotometric determination of amlodipine besylate and hydrochlorothiazide in tablet form [170]. Simultaneous equation spectrophotometric method was used for estimation of hydrochlorthiazide in bulk and pharmaceutical formulations. The absorbance was measured at λ max of 271nm for hydrochlorothiazide after dissolving in methanol [171]. First order derivative spectrophotometric method was described for determination of nebivolol and hydrochlorothiazide in tablets .The absorbance was measured at 270 nm and 282 nm for nebivolol and hydrochlorothiazide, respectively [172]. Oxidation of hydrochlorothiazide by ammonium metavanadate formed complex which was measured spectrophotometrically at λ max 365 nm [173].

Literature Review
Another UV spectrophotometric method for determination of hydrochlorothiazide and valsartan in solid dosage forms was described. This method was based on dissolving drugs in methanol then absorbance was measured at 271 nm for hydrochlorothiazide [174]. Two spectrophotometric methods were presented for estimation of atenolol and hydrochlorothiazide in combined an isoabsorptive point at 287 nm in methanol [178].
UV spectrophotometric method was applied for estimation of hydrochlorothiazide in bulk drug by using 6M urea and 10% citric acid to achieve hydrotropic solubilization of drug in pharmaceutical dosage forms. The absorbance was measured at 272 nm [179].  The separation was carried out on Inertsil ODS C 18 using mixture of 0.01M potassium dihydrogen orthophosphate buffer and acetonitrile (60:40, v/v) as a mobile phase, pH was adjusted to 4.8 with orthophosphoric acid. Drugs were detected at 217 nm [185]. were used for determination telmisartan and hydrochlorotiazide in the commercial pharmaceuticals [188].