Development and validation of an analytical method for the quantitative determination of 2-[2-[(5RS)-5-(hydroxymethyl)-3-methyl-1,3-oxazolidin-2-ylidene]-2-cyanoethylidene]-1H-indol-3(2H)-one in the medicinal product by HPLC-DAD

Introduction. The indolinone derivative 2-[2-[(5RS)-5-(hydroxymethyl)-3-methyl-1,3-oxazolidin-2-ylidene]-2-cyanoethylidene]-1H-indol-3(2H)-one (hereinafter referred to as GRS) is a novel soluble guanylate cyclase stimulator and serves as the active pharmaceutical ingredient in the new antithrombotic drug, capsules 20 mg. In pharmaceutical development and industrial manufacturing of medicinal products, multistage quality control is a determining factor for their efficacy and safety. Therefore, the development and validation of rapid and precise analytical methods is an important scientific and practical task.

Aim. To develop and validate a method for the quantitative determination of the active substance (GRS) in the drug product (capsules, 20 mg) using high-performance liquid chromatography with a diode array detector.

Materials and methods. The study objects included the drug containing GRS, (capsules, 20 mg), excipients used in its manufacturing, and the GRS API (powder). Chromatographic conditions were as follows: Kromasil C18 chromatographic column (250 × 4.6 mm, 5 μm); column oven temperature 40 °C; detection wavelength 372 nm; mobile phase A – acetate buffer (pH 4.0); mobile phase B – methanol. Gradient elution mode was performed over 17 min.

Results and discussion. The developed method has been validated according to the following parameters: specificity, linearity within the analytical range, accuracy, precision, and robustness.

Conclusion. The developed method of high-performance liquid chromatography for the quantitative determination of the active substance GRS in the drug product (capsules, 20 mg), has acceptable validation characteristics and is rapid and simple in terms of sample preparation, which allows it to be used in routine analysis for quality control during production.

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