DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING UPLC METHOD, IDENTIFICATION, AND CHARACTERIZATION OF THREE DEGRADANT IMPURITIES IN PHARMACEUTICAL DOSAGE FORM OF RABEPRAZOLE SODIUM

Abstract

A simple, sensitive, and reproducible ultra performance liquid chromatography (UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of Rabeprazole Sodium and its three potential degradant impurities along with other six impurities in pharmaceutical dosage forms. Three unknown impurities of Rabeprazole, a proton pump inhibitor, were formed in the formulated drug under the stress conditions, [40°C/75% Relative humidity (RH) for 6 months] with relative retention times (RRT's) 0.10, 0.18, and 0.31. A thorough study was undertaken to characterize these potential degradants. These impurities were enriched by using various stressed conditions, isolated using preparative HPLC and characterized by NMR and MS. On the basis of the spectral data, the Impurity-I, II, and III were characterized as 2-Amino-1H-benzimidazole, 1H-Benzimidazol-2-ol, and 2-Benzimidazolethiol. Chromatographic separation was achieved on Acquity UPLC, RP18 column (100 × 2.1 mm i.d., 1.7 µm particle size). The instrument was set at a flow rate of 0.4 mL/min, the column oven temperature was maintained at 25°C, and the eluted compounds were monitored at 280 nm. The resolution between Rabeprazole and its nine impurities was greater than 1.5. Method was validated as per ICH guidelines.

Keywords:

• ICH guidelines
• impurities
• MS
• NMR
• rabeprazole sodium
• UPLC

Notes

^##This column gives the ¹H-¹H multiplicity, s-singlet, dd-doublet of doublet, br-broad, m-multiplet.

^##This column gives the ¹H-¹H multiplicity, s-singlet, br-broad.

^##This column gives the ¹H-¹H multiplicity, m-multiplet, br-broad.