IDENTIFICATION OF PRASUGREL (AN ANTIPLATELET DRUG) IMPURITIES BY LC-MS/MS, RAPID DETERMINATION OF PRASUGREL HYDROCHLORIDE-RELATED SUBSTANCES, AND DEGRADATION PRODUCTS IN ACTIVE PHARMACEUTICAL INGREDIENT AND PHARMACEUTICAL DOSAGE FORMS BY STABILITY INDICATING ULTRA-PERFORMANCE LIQUID CHROMATOGRAPHIC METHOD

Abstract

A simple, sensitive, and reproducible gradient reverse-phase ultra-performance liquid chromatographic (UPLC) method was developed for the quantitative determination of Prasugrel and all possible process-related impurities (positional isomers, degradants and byproducts) at the level of 0.5–2.0 µg mL⁻¹. The main objective of this study is to control the impurities at crude and final stages of prasugrel hydrochloride. This method is applicable to drug substance and pharmaceutical dosage forms. Six potential impurities were formed during the process development, including the degradation products, and the desacetyl impurity existing in its keto and enol form was stabilized by using acidic pH. All these impurities were well separated primarily with a gradient HPLC method, based on their selectivity differences by using a polar embedded C8 column, monobasic potassium buffer, a basic organic modifier, and acetonitrile in the mobile phase. Initially, structures of all these impurities formed were identified by liquid chromatography equipped with mass spectrometer and further confirmed by spiking with the characterized impurities. The drug was subjected to 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.

Keywords:

• forced degradation
• identification by LC/MS/MS
• Prasugrel hydrochloride
• stability-indicating
• UPLC
• validation

ACKNOWLEDGMENT

The authors wish to thank the management of Dr. Reddy's group for supporting this work. They also wish to thank Mr. G. Goverdhan, Mr. A. Sampath, and Ch. Krishnaiah of the Process research group for providing the samples for our research and continuous support.

Notes

^a Mean ± SD (n = 6).

^b Relative retention times (RRT) were calculated against the retention time (RT) of Prasugrel.

^c Resolutions were calculated between two adjacent peaks.

ND, not detected.

^a Mass balance: (% assay + % sum of all compounds + % sum of all degradants).