Combined DNA, toxicological and heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional Chinese medicine (TCM)

Megan L Coghlan, Garth Maker, Elly Crighton, James Haile, Dáithí C Murray, Nicole E White, Roger W Byard, Matthew I Bellgard, Ian Mullaney, Robert Trengove, Richard J N Allcock, Christine Nash, Claire Hoban, Kevin Jarrett, Ross Edwards, Ian F Musgrave, Michael Bunce, Megan L Coghlan, Garth Maker, Elly Crighton, James Haile, Dáithí C Murray, Nicole E White, Roger W Byard, Matthew I Bellgard, Ian Mullaney, Robert Trengove, Richard J N Allcock, Christine Nash, Claire Hoban, Kevin Jarrett, Ross Edwards, Ian F Musgrave, Michael Bunce

Abstract

Globally, there has been an increase in the use of herbal remedies including traditional Chinese medicine (TCM). There is a perception that products are natural, safe and effectively regulated, however, regulatory agencies are hampered by a lack of a toolkit to audit ingredient lists, adulterants and constituent active compounds. Here, for the first time, a multidisciplinary approach to assessing the molecular content of 26 TCMs is described. Next generation DNA sequencing is combined with toxicological and heavy metal screening by separation techniques and mass spectrometry (MS) to provide a comprehensive audit. Genetic analysis revealed that 50% of samples contained DNA of undeclared plant or animal taxa, including an endangered species of Panthera (snow leopard). In 50% of the TCMs, an undeclared pharmaceutical agent was detected including warfarin, dexamethasone, diclofenac, cyproheptadine and paracetamol. Mass spectrometry revealed heavy metals including arsenic, lead and cadmium, one with a level of arsenic >10 times the acceptable limit. The study showed 92% of the TCMs examined were found to have some form of contamination and/or substitution. This study demonstrates that a combination of molecular methodologies can provide an effective means by which to audit complementary and alternative medicines.

Figures

Figure 1. Summary of traditional Chinese medicines…
Figure 1. Summary of traditional Chinese medicines (TCMs) tested in this study that contained toxic metals, undeclared or illegal contents as determined by DNA, toxicological, and heavy metal screening methods.
Each TCM tested is represented in the diagram as a tablet; blue shading on tablets indicate AUST L listed medicines, red shading are not-listed with the TGA regulatory body. TCMs deemed non-compliant for DNA (green), toxicology (pink) and heavy metals (yellow) or a combination thereof, are represented within the Venn diagram. ‘Non compliance’ is defined as containing an illegal or undeclared species, undeclared pharmaceutical, or heavy metal in quantities beyond the allowable daily dosage limit. Two TCM’s were classified as ‘undetected’ using the testing methods described.

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