Eco-friendly spectrophotometric evaluation of triple-combination therapies in the treatment strategy of patients suffering from hypertension during coronavirus pandemic - Spectralprint recognition study

Abstract

Recent studies have reported that using certain antihypertensive therapies such as angiotensin II receptor blockers (ARBs) and calcium channel blocker (CCBs) is associated with reduction of fatal outcomes and improving clinical characteristics of patients suffering from hypertension during coronavirus pandemic. Thus, in the current work an effective, innovative and eco-friendly spectrophotometric manner namely, parent spectrum extraction (PSE)was established for evaluation of recommended triple antihypertensive combination therapies incorporate valsartan (VAL) as ARBs, amlodipine besylate as CCBs (AML) and hydrochlorothiazide (HCT)as diuretic into single-pill in challengeable ratio. PSE manner composed of two complementary steps, auxiliary resolution coupled with data analysis resolution(DAR)and it is characterized by resolving the spectral bands of the drugs and extraction of their discrete parent spectra (D⁰); accordingly, enabling determination of each analyte at its λ_max. Auxiliary resolution of AML in triple mixture was applied to decrease complexity of overlapped spectra via constant multiplication (CM) followed by spectrum subtraction (SS) to obtain resolved mixture of VAL and HCT while data analysis resolution (DAR) of this binary mixture was applied via one of three novel methods namely, absorbance extraction (AE), peak-amplitude extraction (PE) and ratio extraction (RE) along with SS method. The proposed methods had analyzed VAL, AML and HCT in the range of 4.0-44.0 µg/mL, 4.0-40.0 µg/mL and 2.0-24.0 µg/mL, respectively with an excellent correlation coefficient (r ≥ 0.9999). Further, the proposed methods in PSR manner were validated as stated by ICH guidelines and it was found that accuracy and precision results are within the acceptable limit. The suggested procedures were effectively utilized for the concurrent quantification of VAL, AML and HCT in synthetic mixtures and tablets. The greenness of the proposed spectrophotometric methods was evaluated by National Environmental Methods Index (NEMI), the Analytical Eco-Scale, the Green Analytical Procedure Index (GAPI) and Analytical greenness metric (AGREE) where the four tools affirmed the eco-friendly nature of the proposed methods. A comparison between the outcomes of the studied methods with the official and reported ones was performed and no statistical difference was arisen between the methods regarding to accuracy and precision.The achieved results along with the simplicity, affordability and low-cost of the proposed methods recommended their appropriateness for the regular quality control examination and analysis of pure materials and pharmaceutical formulations as well as their applicability for the spectralprint recognition of the studied drugs.

Keywords: Absorbance extraction; Eco-friendly; Parent spectrum extraction; Peak-amplitude extraction; Ratio extraction; Spectralprint recognition.

Graphical abstract

Fig. 1

The chemical structures of the proposed drugs: (a) Valsartan, (b) Amlodipine besylate and (C) Hydrochlorothiazide.

Diagram 1

Representing the effect of antihypertensive medicines on clinical characteristics and fatal findings in COVID-19 patients.

Fig. 2

Parent zero order absorption spectra of VAL (----) 16.0 µg/mL, AML (.....) 6.0 µg/mL and HCT (—) 2.5 µg/mL.

Fig. 3

Resolved zero order absorption spectra of the binary mixture of VAL (----) 16.0 µg/mL and HCT (—) 2.5 µg/mL showing absorbance factor using λ₁ (270.5 nm) and λ₂ (330 nm).

Fig. 4

Resolved ratio spectrum of the binary mixture of VAL (----) 16.0 µg/mL and HCT (—) 2.5 µg/mL using AML 28.0 µg/mL as a divisor showing amplitude factor using λ₁(274.5 nm) and λ₂ (330 nm).

Fig. 5

Resolved ratio spectrum of the binary mixture of VAL (----) 16.0 µg/mL and HCT (—) 2.5 µg/mL using VAL 28.0 µg/mL as a divisor showing the selected λ₁ (275 nm) and λ₂ (250 nm).