Development of a specific and sensitive high-performance thin-layer chromatography assay method for the determination of linagliptin in tablet dosage form

Abstract

Linagliptin (LIN) is an inhibitor of the enzyme dipeptidylpeptidase 4 (DPP4) used for the treatment of diabetes [1]. Chemically, it is 8-[(3R)-3-amino-1-piperidinyl]-7-(2-butyn1-yl)-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]-3,7-dihydro-1H-purine-2,6-dione (Fig. 1) [2]. LIN (Tradjenta) is marketed in tablet formulation. Literature review reveals that there are a number of methods available to estimate the drug by ultraviolet (UV) methods [3], high-performance liquid chromatography (HPLC) methods [4‒7] in single and in combination with metformin and high-performance thin-layer chromatography (HPTLC) methods for stability-indicating study [8‒9]. However, the reported HPTLC methods for LIN show very complicated mobile phase. The International Council for Harmonisation (ICH) guideline Q1A (R2) for parent drug stability-indicating test recommends that stress testing on the drug could be performed to ascertain the stability characteristics of the drug and to support the suitability of the proposed analytical method [10‒12]. It is suggested to carry out the stress testing to determine the effects of temperature, light, oxidizing agents and effect of a wide range of pH values. These facts led us to develop a validated stability-indicating HPTLC method that can be used effectively to determine LIN and the possible degradation products in tablet dosage form. 2 Experimental