Development of a robust SFC method for evaluation of compatibility for a novel antituberculotic fixed-dose combination

摘要: A fast and simple supercritical fluid chromatography method for the simultaneous determination of two antituberculotic drugs, isoniazid rifabutin, their impurities from a new proposed fixed-dose combination (FDC) was developed. Isoniazid rifabutin are used in therapy as single active substance medications. Although FDCs have proved beneficial general, compatibility issues some combinations been reported. The development suitable analytical was, therefore, necessary to assess applicability these substances FDC formulation. Two components related compounds were successfully separated only 7 min using an Acquity UPC2™ Torus DEA, 130 A, 1.7 μm, 3.0 × 100 mm column. Compressed CO2 modified with mixture methanol–2-propanol–water–triethylamine, ratio 70 : 28 : 2 : 0.1 (v/v/v/v), obtain gradient elution. Quality-by-design principles implemented accomplish reliable robust method. Modeling software (JMP®, version 13.2.1) utilized Design Experiments. Mathematical models relationship column temperature, pressure, modifier composition flow rate five critical quality attributes generated. comprehensive approach facilitated detection influencing factors significant second-order terms indicating factors' interaction nonlinear effects. validated specificity, linearity, sensitivity, accuracy, precision, stability, filter study robustness compliance internationally accepted guidelines. Acceptable validation results obtained both concentration level ranges (assay determination). Finally, tested commercially available samples substances.