Sequential design of experiments approach for the multiproduct analysis of cholesterol‐lowering drugs by ultra‐high‐performance supercritical fluid chromatography

Abstract

A multiproduct approach toward method development is presented for a fast and reliable analysis of the eight most important cholesterol-lowering drugs via ultrahigh-performance supercritical fluid chromatography. A two-step approach based on design of experiments was applied: (1) selection of the stationary phase, organic modifier, and diluent in the mobile phase through a multilevel categorical design and (2) optimization of the elution strength by varying the pressure, temperature, and gradient using a central composite design. Finally, the flow rate was adjusted. The first design selected UPC 2 Torus 1-AA as the column, ethanol:water as the organic modifier, and acetonitrile:ethanol 3:2 v/v as the diluent. The results led to a pressure, column temperature, and gradient elution of 14.83 MPa, 42 • C, and 5-15.5% of ethanol:water in CO 2 , respectively. The flow rate was set at 1.8 mL/min, providing a total analysis time of 4 min. This multiproduct method was validated and applied to 11 different commercial products available in the Brazilian market, and it was found to be accurate, with r > 0.990, recoveries between 95 and 105%, and precision not higher than 5.4%. Therefore, this method was shown to be a greener alternative for the analysis of these pharmaceuticals.

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.…”

“…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.…”

Development and validation of ultra‐high performance supercritical fluid chromatography method for quantitative determination of six compounds in Guizhi Fuling capsule and tablet samples

“…Ultra‐high performance supercritical fluid chromatography (UHPSFC), which uses supercritical carbon dioxide (CO 2 ) as the principal solvent that could offer several advantages over traditional LC and GC [1, 2]. These advantages include: (1) the low viscosity of CO 2 allows higher flow rates and achieves faster run times, (2) the higher diffusivity of compounds in supercritical CO 2 could achieve high‐efficiency separation, and (3) the UHPSFC can significant reduces the use of organic solvents, which meet the requirement of green chemistry [3, 4]. The applications of UHPSFC in the fields of pharmaceutical analysis have been described by many researchers [5–7].…”