Quantitative Simultaneous Determination of Fenofibrate, Atorvastatin, and Ezetimibe in Tablets Using Gradient High-Performance Column Liquid Chromatography and High-Performance Thin-Layer Chromatography

Abstract

& Simple, accurate, precise, sensitive, and validated high-performance liquid chromatography (HPLC) and high-performance thin-layer chromatography (HPTLC)-densitometric methods were developed for simultaneous determination of fenofibrate (FEN), atorvastatin (ATO), and ezetimibe (EZE) in combined tablet dosage form. In Method A, the gradient RP-HPLC analysis was performed on a Shim-pack C18 column (150 Â 6 mm id), using a mobile phase consisting of 0.1% formic acid and acetonitrile in solvent gradient elution for 25 min at a flow rate of 1.5 mL min À1 . Quantification was carried out using a photodiode array UV detector at 245 nm. The employment of diode array detector allowed selectivity confirmation by peak purity evaluation. In Method B, the HPTLC analysis was carried out on an aluminum-backed sheet of silica gel 60F 254 layer using toluene: methanol:triethylamine (8:1.5:0.1, v=v=v) as the mobile phase. Quantification was achieved with UV densitometry at 245 nm. The analytical methods were validated according to International Conference on Harmonization guidelines. Low relative standard deviation values indicated good precision. Both the methods were successfully applied for the analysis of drugs in laboratory-prepared mixtures and commercial tablets. No chromatographic interference from tablet excipients was found, and hence these methods are applicable for simultaneous determination of FEN, ATO, and EZE in pharmaceutical formulations.

Development of a sustainable multianalyte MEKC method for quantitation of the antihyperlipidemic drugs ezetimibe together with three statins. Greenness and whiteness appraisal studies

“…Commonly, MEKC is greener than other spectrophotometric and chromatographic techniques including HPLC and HPTLC due to the minute amount of solvent used and nearly no waste produced. The pictograms displayed in Table 5 corroborated the top-ranking greenness of the optimized MEKC method with a score of 0.95 followed by GC-FID [ 60 ] (0.86), the spectrophotometric method [ 22 ] (0.77), HPTLC [ 62 ] (0.76), HPLC [ 60 ] and UHPSFC [ 61 ] (both 0.73) and finally UPLC-Q-TRAP/MS [ 63 ] (0.68). It is worth noticed that although UHPSFC and UPLC-Q-TRAP/MS are considered greener versions of HPLC due to low consumption of organic solvents and low waste production, however, they are highly consuming energy especially UPLC-Q-TRAP/MS due to mass detector in addition to their inaccessibility.…”

“…The trendiest metrics used were the Analytical GREEnness Metric Approach and Software (AGREE) [ 45 , 56 – 59 ] and the RGB 12 model [ 3 , 58 , 59 ]. The proposed method was compared in the matter of greenness and whiteness with different selected reported techniques: spectrophotometry [ 22 ], HPLC–UV [ 60 ], gas chromatography with flame ionization detection (GC-FID) [ 60 ], ultra‐high‐performance supercritical fluid chromatography (UHPSFC) [ 61 ], HPTLC [ 62 ] and ultra-performance liquid chromatography-tandem triple quadrupole compound linear ion trap mass spectrometry (UPLC-Q-TRAP/MS) [ 63 ].…”

“…Regarding validation criteria (red area), the largest scope of application is found in the reported UHPSFC [ 61 ] and HPLC [ 60 ] followed by the proposed MEKC method. All the methods are found accurate and precise since they followed the ICH recommendations, except the UHPSFC method [ 61 ] which adopted the Brazilian Health Regulatory Agency (ANVISA) guidelines and UPLC-Q-TRAP/MS [ 62 ] that followed the FDA bioanalytical method validation. In addition, the GC-FID method [ 60 ] had the lowest score in terms of validation criteria because the study lacks the full analytical data such as linearity, accuracy, precision and application in dosage forms of all drugs investigated in the study, actually, only EZE was considered which was measured in a linearity range of 39.98–999.60 μg/mL with strangely high LOD 19.992 μg/mL.…”

“…The green area exposed that the developed MEKC platform was the greenest with the minimum amount of reagents and waste production and lowest energy consumption followed by GC-FID [ 60 ], spectrophotometry [ 22 ], HPTLC [ 62 ], HPLC [ 60 ], UHPSFC [ 61 ] and finally UPLC-Q-TRAP/MS [63]. Noticeably, the aforementioned results elucidated the harmony with the AGREE assessment.…”