A Novel Stability Indicating High Performance Liquid Chromatography Method for Lysergic Acid Diethylamide Quantification: From Microdosing Applications to Broader Analytical Use

With the rising interest in therapeutic potential of microdosing lysergic acid diethylamide (LSD), accurate quantification and stability analysis are imperative for both scientific research and end-user safety. Currently, high throughput quantification of LSD in clinical microdosing formulations and community sourced microdosing samples remain a challenge due to the absence of fast analytical methods. This study aimed to develop a robust, stability indicating, isocratic reverse-phase-high performance liquid chromatography (RP-HPLC) method for the accurate and precise quantification of LSD. Importantly, the method was capable of separating LSD from its primary-degradation product, iso-LSD. Adhering to International Conference on Harmonization guidelines, the method was validated for various parameters such specificity, linearity, accuracy, precision, limit of detection (LOD), limit of quantification (LOQ) and robustness. The developed method proved its efficacy in quantifying LSD even in the presents of degradants induced by various recommended stress conditions. This method was applied to quantify LSD in illicit microdosing samples obtained from New Zealand's unique community drug checking service and found a significant discrepancy between user-estimated and actual LSD levels. This highlights the method's critical importance in providing reliable data for the safety and quality control of LSD microdosing in pharmaceutical and illicit formulations and highlights potential risks for users in using non-pharmaceutically prepared microdosing formulations.