The importance of standardisation in phytomedicine: Variation in mood-enhancing mesembrine-alkaloids in non-standardised vs. Zembrin® commercial products

• Psychoactive mesembrine-alkaloids are found in Mesembryanthemum tortuosum • A standardised extract Zembrin ® was developed to ensure consistent quality • Twelve commercial products were analysed for alkaloid content by HPLC • The Zembrin ® products' result were very similar and within clinically tested ranges • The remaining products showed an up to 1600-fold difference in mesembrine content Mesembryanthemum tortuosum , commonly known as kanna, is traditionally used as a mood enhancer due to its mesembrine alkaloids, notably mesembrine and mesembrenone, which demonstrate anxiolytic and antidepressant properties. Zembrin®, a patented standardised extract, seeks to ensure a consistent alkaloid content in products like Elev8™ and Zerenity™, supporting reliable efficacy. However, many non-standardised over-the-counter products, with variable and unspecified alkaloid levels, are widely available, potentially leading to inconsistent therapeutic outcomes. This study aimed to develop and validate an HPLC method to quantify mesembrine and mesembrenone and assess the variability of alkaloid content in commercially available products, including those containing Zembrin®. A comparative analytical study was conducted to evaluate the alkaloid content of 12 commercially available M. tortuosum products, two of which contained Zembrin® and six different batches of one Zembrin® containing product, using the newly developed HPLC method. A HPLC method was developed and validated to quantify mesembrine and mesembrenone. The technique was used to analyse 18 over-the-counter M. tortuosum products, including two containing Zembrin® and six different batches of one standardised product. Alkaloid concentrations, labelling accuracy, and dosage instructions were assessed. The two Zembrin®-containing products, despite different formulations and manufacturers, contained mesembrine (32 vs. 27 µg/max daily dose) and mesembrenone (91 vs. 108 µg/max daily dose), which fall within clinically tested dosages . In contrast, significant variability was observed in the non-standardised commercial products, with mesembrine and mesembrenone differing by over 1,600-fold (17 714 vs. 11 µg/max daily dose) and 70-fold (1 514 vs. 20 µg/max daily dose), respectively. The inter-batch results of the standardised product demonstrated remarkable consistency across all batches tested, with relative standard deviations of only 2.3 and 3.1% for mesembrine and mesembrenone, respectively. The HPLC method effectively quantified mesembrine and mesembrenone, revealing substantial variability in non-standardised M. tortuosum products. The remarkable consistency of Zembrin®-containing products underscores the importance of standardisation and highlights the critical need for quality control in phytomedicines.