Berberine from Berberis aristata: How stable isotope analysis enables the discrimination between natural and synthetic origins

Berberine is a benzylisoquinoline alkaloid traditionally sourced from plants such as Berberis aristata and Coptis chinensis , widely used for its therapeutic properties. However, the high cost of natural extraction has led to the increasing use of cheaper synthetic berberine derived from petrochemical sources, raising concerns over product authenticity. This study investigates the stable isotope composition ( δ ¹³C, δ ¹⁵N, δ ²H, δ ¹⁸O) of natural berberine extracted from Berberis aristata and synthetic samples produced through unknown chemical routes, likely involving catechol-based starting materials, using isotope ratio mass spectrometry (IRMS). Among the tested isotopic parameters, δ ¹³C proved the most reliable for origin discrimination, with natural berberine showing significantly lower values (–33‰ to –32‰) than synthetic products (–30.6‰ to –29.7‰). δ ²H provided complementary differentiation, although variability in synthetic pathways can produce partial overlap with natural products. Conversely, δ ¹⁵N and δ ¹⁸O displayed limited discriminating power due to overlapping ranges. A market survey of low-cost commercial berberine supplements labelled as natural revealed that most samples matched isotopic values typical of synthetic berberine, indicating widespread undeclared substitution. These findings highlight the importance of stable isotope analysis as a robust tool for authenticity verification and quality control of botanical ingredients in consumer products.