Details

Autor(en) / Beteiligte

• Malati, Vakamulla
• Raghupati Reddy, Anumala
• Mukkanti, K.
• Suryanarayana, M.V.

Titel

A novel reverse phase stability indicating RP-UPLC method for the quantitative determination of fifteen related substances in Ranolazine drug substance and drug product

Ist Teil von

• Talanta (Oxford), 2012-08, Vol.97, p.563-573

Ort / Verlag

Amsterdam: Elsevier B.V

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• A gradient reverse-phase ultra performance liquid chromatographic (RP-UPLC) method was developed for the quantitative determination of Ranolazine and potential process-related impurities (starting materials, positional isomers, degradants and byproducts) at the level of 0.1μgmL−1 to 0.3μgmL−1. Fifteen potential impurities were identified in the crude samples during the process development. Tentative structures for all the impurities were assigned based on m/z values from LC-MS/MS analysis. This method can be used for the quality control of both drug substance and drug product. All these impurities were separated with a gradient UPLC method by using a polar embedded Waters Acquity BEH RP18 100mm×2.1mm,1.7μm column, monobasic sodium buffer, a basic organic modifier and acetonitrile in the mobile phase. Further, this method is also capable of separating a major oxidative degradant Di-N-oxide. Impurities having electron donating groups(+I effect) on the phenyl ring increased the retention by improved п–п interactions. The drug was subjected to the International Conference on Harmonization (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness. ► Separation of 15 process related impurities with in 15min. ► New stability indicating method for Ranolazine by using UPLC. ► Method has capability of separating major oxidative degradant di-N-Oxide impurity. ► New method for the separation of regio isomers of Ranolazine. ► designed to determine impurities in drug substance as well as in the drug product.