Forced Degradation of Cannabidiol CBD

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Forced Degradation of Cannabidiol CBD ( forced-degradation-cannabidiol-cbd )

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[ APPLICATION NOTE ] APPLICATION BENEFITS ■■ The ACQUITY UPLC® H-Class and the ACQUITY UPC2® Systems are highly reliable instruments that can be used to orthogonally monitor the stability of CBD by reversed-phase liquid chromatography (RPLC) and UltraPerformance Convergence Chromatography,TM respectively. ■■ The ACQUITY UPLC H-Class System separates closely eluting Δ9-THC and Δ8-THC by reversed-phased chromatography, while the ACQUITY UPC2 System further separates THC compounds based upon their stereochemistry. ■■ The ACQUITY UPLC PDA Detector and ACQUITY® QDa® Detectors are useful tools that provide spectral and mass information for the identification of unknown compounds and degradation products. ■■ The Waters® Fraction Manager – Analytical (WFMA) can be used to collect degradation product peaks separated at the UPLC® scale for additional analysis. WATERS SOLUTIONS ACQUITY UPLC H-Class System ACQUITY UPC2 System ACQUITY QDa Detector ACQUITY UPLC PDA Detector Waters Fraction Manager - Analytical (WFM-A) Empower® 3 Chromatography Data Software TrefoilTM Columns ACQUITY UPLC Columns KEYWORDS Cannabidiol, CBD, Tetrahydrocannabinol, THC, Cannabis, Cannabinoid, Hemp, Forced degradation, Chiral Forced Degradation of Cannabidiol Catharine Layton, Jacquelyn Runco, and Andrew Aubin Waters Corporation, Milford, MA, USA INTRODUCTION The debate surrounding the use of cannabinoids for medicinal purposes has been in the news for several years. Although there are at least 85 active substances identified in cannabis, many people associate the bio-botanical with the psychoactive compound tetrahydrocannabinol (THC). Recent attention has shifted to the non-psychoactive compound cannabidiol (CBD), as evidence of the medical benefits continue to grow.1 Some CBD preparations are marketed as dietary supplements and claim efficacy against a range of medical conditions. For manufacturers of these preparations, it is important to monitor product stability. A change in this parameter risks consumer health and safety when toxic or unexpected degradation products form over time resulting in the delivery of a different CBD dose than expected.2 Extracts prepared from cannabis products can pose a significant challenge to chromatographers due to the vast number of naturally occurring cannabinoid structural isomers.3 When analyzing complex mixtures, it is beneficial to employ multiple strategies and utilize various analytical tools to provide a more comprehensive understanding of the components within the mixture. For example, when applying different modes of separation, one may gain additional knowledge of both the compounds present and their structural composition. Through a preliminary forced degradation study of crystalline CBD, we demonstrate how UPLC and UPC2 can be applied collectively to monitor solution stability. The ACQUITY UPLC H-Class instrument uses conventional reversed-phase chromatography, while the ACQUITY UPC2 system provides a stereo-chemical separation of important structural isomers via convergence chromatography. When these techniques are coupled with photo diode array (PDA) and mass spectrometry (MS), the chemical and structural identity of important CBD degradation products is determined. 1

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