(M1330-04-24) High-Performance Liquid Chromatography Method with Refractive-Index Detection for Quantitation of Memantine Hydrochloride in Memantine Hydrochloride Extended-Release Dissolution Samples

Purpose: The cUSP Memantine Hydrochloride Tablets Monograph: Dissolution utilizes an internal standard, liquid-liquid extraction, and GC-FID for analysis. The FDA Dissolution Database for Memantine Hydrochloride Capsules (Extended-Release) outlines dissolution parameters but does not include a mode for analysis. The present study was aimed to optimize and/or develop an analytical method for quantitation of memantine hydrochloride in memantine hydrochloride extended-release capsules in dissolution samples using high-performance liquid chromatography as an alternative mode of analysis and to simplify the sample preparation post dissolution sampling (i.e. removal of the internal standard and liquid-liquid extraction).

Methods: Chromatographic separation was achieved on a Waters XBridge C18, 4.6 mm x 250 mm, 3.5 μm particle size column maintained at 35 °C, employing mobile phase consisting of 1.0% diethylamine in water (pH 5.2):methanol (35:65 v/v) pumped at a flow rate of 1.0 mL/min. Detection by refractive-index was performed and the retention time of memantine hydrochloride was found to be approximately 4.7 minutes.

Results: The chromatographic method was qualified and found to be linear over the concentration range of 0.5 – 32 µg/mL for memantine hydrochloride with potential to support low strength drug products. The method was found to be specific and repeatable for the quantitation of memantine hydrochloride in memantine hydrochloride extended-release capsules in dissolution samples.

Conclusion: The method provides a simpler, more QC-friendly option for routine quantitation of memantine hydrochloride in memantine hydrochloride extended-release dissolution samples.

References: Sawant, Tukaram & Wakchaure, Sandip & Rakibe, Udyakumar & Musmade, Prashant & Chaudhari, Bhata & Mane, Dhananjay. (2017). The Development and Validation of Novel, Simple High-Performance Liquid Chromatographic Method with Refractive Index Detector for Quantification of Memantine Hydrochloride in Dissolution Samples. Journal of chromatographic science. 55. 1-7. 10.1093/chromsci/bmx013.