Abstract

A highly sensitive three-dimensional excitation-emission fluorescence method was proposed to determine antihypertensives including valsartan and amlodipine besylate in human plasma with the aid of second-order calibration methods based on parallel factor analysis (PARAFAC) and alternating trilinear decomposition (ATLD) algorithms. Antihypertensives with weak fluorescent can be transformed into a strong fluorescent property by changing microenvironment in samples using micellar enhanced surfactant. Both the adopted algorithms with second-order advantage can improve the resolution and directly attain antihypertensives concentration even in the presence of potential strong intrinsic fluorescence from human plasma. The satisfactory results can be achieved for valsartan and amlodipine besylate in complicated human plasma. Furthermore, some statistical parameters and figures of merit were evaluated to investigate the performance of the proposed method, and the accuracy and precision of the proposed method were also validated by the elliptical joint confidence region (EJCR) test and repeatability analysis of intraday and interday assay. The proposed method could not only light a new avenue to directly determine valsartan or amlodipine besylate in human plasma, but also hold great potential to be extended as a promising alternative for more practical applications in the determination of weak fluorescent drugs.

Highlights

  • Hypertension is considered as a chronical disease resulting in the elevation of arterial hypertension and increasing the risk of cardiac disease [1]

  • To investigate the fluorescent properties of the valsartan and amlodipine besylate, the pure valsartan and amlodipine besylate were prepared and measured via fluorescence spectrophotometer at the given parameters; Figures 1(a) and 2(a) show valsartan and amlodipine besylate with weak fluorescence, which is hard to determine at the low concentration due to matrix effect, requiring researchers to adopt possible ways, namely, micellar enhanced spectrofluorometric method to increase the fluorescence of two analytes; sodium dodecyl sulfate (SDS), a kind of surfactant, is to stabilize and enhance the fluorescence intensity of both valsartan and amlodipine besylate; it can be safely observed that the fluorescence intensity of both analytes has remarkably increased as shown in Figures 1(b) and 2(b)

  • A serious profile overlapping between the valsartan and human plasma together with amlodipine besylate and human plasma was experimentally observed, which made the quantitative analysis of the two analytes using traditional fluorescent methodologies impossible; one can resort to the second-order calibration methods which allow for unique decomposition of trilinear data and only require that the species of interest in both calibration samples and the prediction samples are the same, so with the aid of chemometrics the interference of human plasma can be mathematically separated and accomplish reliable resolution of spectra and accurate quantification of valsartan and amlodipine besylate in complicated biological matrix

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Summary

Introduction

Hypertension is considered as a chronical disease resulting in the elevation of arterial hypertension and increasing the risk of cardiac disease [1]. The relationship between pharmacological reduction in blood pressure for hypertensive individuals and decreasing the risk of suffering cardiovascular and renal complications has been known for more than half century [2]. Valsartan selectively inhibits the binding of Angiotensin II to the Angiotensin I receptor in many tissues including vascular smooth muscle and the adrenal gland and blocks vasoconstriction as well as aldosterone-secreting effects of Angiotensin II, reducing blood pressure [6,7,8,9]. Amlodipine, a derivative of dihydropyridines, blocks calcium influx into vascular smooth muscle and cardiac muscle, leading to a decrease in peripheral vascular resistance [10,11,12]. In order to further investigate the pharmacokinetics of valsartan and amlodipine, the analytical methods with regard to valsartan and amlodipine

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