Quantitative Determination of Semaglutide Extracted from Dissolvable Microneedles by a Developed and Optimized LC-MS/MS Method

Abstract

Dissolvable microneedle drug delivery systems have emerged as a promising platform for painless self-administration of biologics such as semaglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of obesity and type 2 diabetes. However, during the manufacturing processes involved in microneedle production, such as polymer mixing, casting, and drying, semaglutide is exposed to thermal, mechanical, and chemical stresses that may lead to degradation or loss of bioactivity. Although previous studies have mainly focused on evaluating delivery efficiency, a rigorously validated method for accurate quantification of semaglutide content in dissolvable microneedle matrices remains urgently needed. In this study, we developed and optimized a sample preparation procedure and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis method for accurate quantification of semaglutide extracted from dissolvable microneedle arrays. The sample preparation focused on maximizing extraction recovery while minimizing drug degradation, and the LC-MS/MS analysis method was optimized for sensitive and reliable detection. This integrated analytical approach is expected to provide an important foundation for ensuring dose uniformity, monitoring formulation stability, and supporting further development and clinical application of semaglutide-containing microneedle therapeutics.