Adulterants and contaminants in psychotropic herbal medicines detected with mass spectrometry and Next-Generation DNA sequencing

Introduction The role of herbal medicine in the treatment of common psychiatric disorders such as anxiety, depression and insomnia has become more established over the past decade. Some herbal preparations such as St John’s wort (Hypericum perforatum) have demonstrated clinical evidence but have also been included in recent reports of widespread adulteration and contamination. Herbal medicines sold in Australia are required to be listed on the Therapeutic Goods Administration’s (TGA) Australian Register of Therapeutic Goods (ARTG) and must comply with strict ingredient and manufacturing guidelines to assure quality and safety. Objective The aim of this research was to assess whether pharmaceutical adulterants and contaminants were present in psychotropic herbal medicines available in Australia, as a measure of quality, and the effectiveness of regulation. Methods A two-pronged approach combining next-generation DNA sequencing and small-molecule analysis techniques was undertaken to audit a subset of herbal medicines for the presence of prescription medications, illicit drugs, pesticides, herbicides, heavy metals and contaminant DNA. Small-molecule analysis included liquid chromatography with quadrupole time-of-flight mass spectrometer (LC-QTOF-MS) detection, liquid chromatography with UV/vis diode array (LC-UV) detection, gas chromatography with nitrogen–phosphorus and mass spectrometer detection (GC-NPD/MS) and heavy metal analysis using inductively coupled plasma with mass spectrometer (ICP-MS) detection. Results In total, 49% (29 of 59) of the investigated herbal medicines had one or more materials not listed on their labels or ARTG registration, including Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES)-listed material (one medicine), heavy metals (12%) or components that could trigger food sensitivity, such as wheat (12%). In contrast to previous studies, no prescription pharmaceutical adulterants were detected, although 10% had undeclared caffeine. Twenty-four percent of herbal medicines had DNA from animal species, including mice and bats, indicating poor quality control. The surveyed herbal medicines included both traditional Chinese medicines (TCM) and Western herbals. Ninety-four percent of TCMs were contaminated or adulterated, compared with 37% of the Western herbals. Only two of the 59 samples contained the listed active ingredient(s) without additional adulterants and contaminants, or missing ingredients. Conclusions The high levels of contamination found in this study suggests that closer surveillance of herbal medicines is needed in order to assure the required level of quality of herbal medicines available in Australia. The results suggest that the TGA’s low-/high-risk system for regulation coupled with post-market auditing is not keeping unapproved and/or unsafe herbal medicines from the market