Development and Validation of Stability Indicating HPLC Method for the Determination of Process and Degradation Related Impurities in Telmisartan Drug Substance

A new sensitive, specific, precise and accurate stability indicating reverse phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for the determination of related substances of telmisartan drug substance. The method was developed to separate possible degradation and process related impurities. The method was developed on symmetry shield RP 8 (150 mm x 4.6 mm, 3.5 µm) column using 0.05% trifluoroacetic acid and acetonitrile as mobile phase in gradient elution. The eluents were monitored at 230 nm by UV-Visible detector. Telmisartan and its eleven impurities were well resolved by using these conditions. The limit of detection (LOD) for telmisartan and each of its impurities (Impurity-II, Impurity-III, Impurity-IV, Impurity-V, Impurity-VI, Impurity-VII, Impurity-IX, Impurity-X, Impurity-XI) were 0.01 (% w/w) and that of Impurity-I, Impurity-VIII were 0.02 (% w/w). The limit of quantitation (LOQ) for telmisartan and each of its impuries (Impurity-II, Impurity-III, Impurity-IV, Impurity-V, Impurity-VI, Impurity-VII, Impurity-IX, Impurity-X, Impurity-XI) were 0.03 (% w/w) and that of Impurity-I and Impurity-VIII peaks were 0.05 (% w/w). Forced degradation studies were performed and mass balance was established for acid, base, oxidative, photolytic, thermal and temperature and humidity degradation conditions. The method was validated as per international conference on harmonization of technical requirements for pharmaceuticals for human use (ICH) guidelines. The impurities (Impurity-VI to Impurity XI) were related to route of synthesis and the developed method was capable to quantify these impurities along with impurities (Impurity-I to Impurity-V) as per United States, European pharmacopeia.

Keywords:

Telmisartan drug substance , Validation , ICH , Stability indicating , Forced degradation , RP-HPLC