Synchronous Spectrofluorimetry Coupled with Third-Order Derivative Signal Processing for the Simultaneous Quantitation o

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ORIGINAL ARTICLE

Synchronous Spectrofluorimetry Coupled with Third-Order Derivative Signal Processing for the Simultaneous Quantitation of Telmisartan and Chlorthalidone Drug Combination in Human Plasma Ahmed Elsonbaty 1 & Mohamed A. Hasan 2 & Maya S. Eissa 1 & Wafaa S. Hassan 3 & Sara Abdulwahab 3 Received: 22 August 2020 / Accepted: 14 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract This study is the first to develop and optimize a method for the simultaneous determination of chlorthalidone (CLT) and telmisartan (TEL) in, human plasma samples as well as in their newly released pharmaceutical tablet form, (Telmikind-CT 40®). The method is based on measuring fluorescence intensity, employing synchronous fluorescence mode coupled to thirdorder derivative signal processing, 0.5% w/v cetyl trimethyl ammonium bromide was used as cationic surfactant to enhance the fluorescence signal intensity and improve method sensitivity. The third-order derivative synchronous spectra of CLT and TEL are well separated with two zero-crossing points which allowed for the determination of CLT and TEL at 362 nm and 351 nm, respectively. Different experimental parameters were carefully investigated and optimized, calibration curves were constructed over concentration ranges of 20–1200 ng.mL−1 and 5–800 ng.mL−1 for CLT and TEL respectively. The developed method is simple and rapid, analytical parameters were validated according to ICH guidelines and high sensitivity was achieved as represented by limits of detection (LOD) of 4.69 and 1.58 ng.mL−1 for CLT and TEL respectively. Keywords Third-order derivative . Synchronous spectrofluorimetry; Chlorthalidone; Telmisartan . Hypertension . Drug combination

Introduction Hypertension is a cardiovascular disease characterized by persistent elevation in blood pressure (BP). Affecting an estimate of one billion people worldwide, uncontrolled hypertension leads to sever cardiovascular complications, contributing to approximately 13% of annual death globally [1, 2]. Fortunately, some cases of hypertension can be managed with lifestyle modifications; however, most cases will require pharmacological intervention employing a combination of * Sara Abdulwahab [email protected] 1

Department of Analytical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt

2

Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo 11751, Egypt

3

Department of Analytical Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig P.C.44519, Egypt

antihypertensive agents e.g. calcium channels blockers (CCBs), diuretics, angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor blockers (ARBs) [1, 3]. Inadequate control of BP has been linked to the lack of adherence of patients to free-drug combination therapy— where each BP-lowering agent is administered separately; however, the use of fixed dose combination (FDC) where several BP-lowering agents are combined in a single pill, has re