Identification of related substances in minocycline hydrochloride via 2D-LC-Q-TOF /MS

Minocycline hydrochloride is a semisynthetic tetracycline derivative with a wide range of applications. The related substances significantly influence its efficacy and safety. However, the investigation of potential related substances in minocycline hydrochloride or its products remains incomplete. Herein, a reliable two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF/MS) method was developed for the separation and identification of the related substances in minocycline hydrochloride tablets. Seventeen related substances, including process-related substances and degradation products, were identified based on the chromatographic and mass spectrometric data. Notably, thirteen of these related substances were newly elucidated. Formation mechanisms of these related substances were proposed, and the degradation pathways of minocycline hydrochloride were systematically established. These findings are useful for the quality control of minocycline hydrochloride as well as other tetracycline drugs.