DEVELOPMENT OF STABILITY-INDICATING UPLC METHOD FOR DETERMINING ZOLPIDEM TARTRATE AND ITS PRODUCT RELATED VARIANTS IN DRUG SUBSTANCE AND DRUG PRODUCTS

Abstract

A stability indicating UPLC method was developed for the quantitative determination of Zolpidem Tartrate (ZT) and its product related variants present in drug substance and drug products. The liquid chromatographic separation was achieved on Acquity UPLC HSS T3-C18 column. All the eight potential variants and the drug were eluted within 8 minutes. A narrow range pH gradient, in combination with organic modifier was used to obtain separation (R_s > 1.5) between critical pairs. There was no placebo interference during the determination of analytes. The method had shown a good and consistent recoveries [98.91 ± 0.55 (mean ± RSD)] with a high degree of intra- and inter-day precision (ANOVA: F_Calculated = 0.6498 < F_Critical = 3.6823) for the drug. Linear regression analysis data revealed the best R² values (0.9980–0.9998) and F Siginificance values (p < α = 0.05) for the drug and impurities. The stability-indicating capability of the method was verified by subjecting the drug to hydrolytic, oxidative, photolytic, and thermal stress conditions. LC-MS was used to identify the mass numbers of the degradation products. The m/z values 281 and 227 were matched with zolpidem acid and zolpyridine, respectively. Possible degradation pathways were discussed for the product related variants formed during stress studies.

Keywords:

• degradation products
• pH gradient
• stability-indicating
• UPLC
• validation
• zolpidem tartrate

ACKNOWLEDGMENT

The authors wish to thank the management of Dr. Reddy's group and Mr. B. Hari Ram for supporting this work. Authors wish to acknowledge the Process research group for providing the samples for our research.

Notes

^a : Resolution between Imp-1 and Imp-2.

^b : Resolution between Imp-5 and Imp-6.

^c : Resolution between Imp-6 and ZT.

^a Relative retention times (RRT) were calculated against the retention time (RT) of Zolpidem tartrate.

^b Resolutions were calculated between two adjacent peaks.

^c Mean ± SD (n = 6).

^a ANOVA Results for inter-day precision.

^b Precision intra-day.

^c Inter-day Precision (three days).

Linearity range is LOQ 150% with respect to 50 µg/mL of ZT for impurities.