Development and validation of a quantitative proton NMR method for the analysis of lysergol

Lysergol is an ergot alkaloid present in the seeds of <i>Ipomoea muricata</i> and <i>Ipomoea violacea</i>, which are part of the <i>Convolvulaceae</i> family. It possesses a range of therapeutic properties, including hypotensive activity, psychotropic, analgesic effects, uterus- and gastrointestinal stimulating activities. Additionally, lysergol is also used as a starting material for the synthesis of anti-Parkinson and cognitive-enhancing drugs such as cabergoline and nicergoline. However, the toxicity of ergot alkaloids, including lysergol, underscores the need for precise quantification, as chronic exposure can lead to ergotism, a condition with severe vascular and neurological consequences. Despite its pharmaceutical relevance, lysergol’s potential toxicity and absence of a United States Pharmacopeia (USP) monograph highlight the urgent need for a reliable and standard quantification method. There is a lack of simple, validated analytical methods for the quality of lysergol in bulk drug substances and plant-based formulations. Hence, we aimed to develop a simple, rapid, cost-effective, and non-destructive qNMR method for the quantification of lysergol in both pure and extract forms. Lysergol samples were being characterized by 1D 1H and 2D 1H-C13C HSQC, 6DEPT, 1H COSY and 1H-C13C HMBC. The developed qNMR method demonstrated excellent performance with high specificity, precision (RSD &lt; 2%), accuracy (96.6-100.6%), linearity (r &gt;0.999), low limit of detection (0.05 mg/mL), and limit of quantification (0.15 mg/mL). The method’s robustness further supports its application in routine quality control. Overall, this work presents a novel and efficient qNMR-based quantification for lysergol, addressing an existing analytical gap in pharmaceutical research and quality assurance.