Personally, I’m appalled by the widespread acceptance of natural products as dietary supplements and therapeutics. Even more disturbing is the apparent lack of interest from regulatory agencies. Visiting markets in Hong Kong and Taiwan where raw materials for nutraceuticals are sold only heightens the unease.
That said, drug research that takes advantage of centuries of experience correlating the components of natural products to provide clues for targeted molecular therapeutics has value. Traditional Chinese Medicines (TCMs) are an example. After all, the scientific method does allow observation of efficacy, even if the mechanism of action is not known: the regulatory process adds some assurance of safety.
I’m impressed with the recent paper authored by Bin Guo and colleagues1 at the Key Laboratory of Phytochemical R&D of Hunan Province at Hunan Normal University in Changsha, China. The team has developed a general platform and protocol for determination of contaminants and adulterants in different matrices (tablet, coated pill, gel cap, and liquid).
The method starts with a generic, single-tube multifunction extraction followed by analysis by LC-IT(MSn)/TOF with dual polarity switching. Evaluation with 500 matrix/analyte pairs demonstrated that its combination of retention time, isotopic profile and accurate MSn spectra successfully resolved most coeluting isobarics and isomers in commercial samples. However, screens of commercial samples frequently showed nontarget adulterants and unexpected species.
The new method uses a 12-step generic sample prep protocol that yields a useful assay despite differences in the matrix and the analyte. The authors claim that their single-tube protocol is able to successfully handle a wider range of matrices than other protocols, including specifically QuEChERS. The workflow seems conducive to processing a modest batch (~10) of samples together.
Samples were assayed with gradient elution reversed-phase liquid chromatography (RPLC) with detection with a hybrid LCMS-IT/TOF instrument from Shimadzu (Kyoto, Japan). Ion trap and time-of-flight (TOF) mass analyzers are very fast (~2.5 sec/scan) and thus compatible with the chromatographic peaks, which were typically about 20 sec wide. The ability to quickly switch from positive to negative ESI modes, combined with retention time, isotopic profile and MSn spectra, facilitates analyte identification and estimation using multi-parameter matching with values contained in the user-created database. Throughput is about one sample/hour.
Overall, the assay had a lower limit of confirmation of 0.1 mg/kg (ppm) for 73% of the 500 analyte/matrix pairs studied. Degrading the level of confirmation to 0.4 mg/kg permitted 97% of the analyte/matrix combinations to be studied. Screening of commercial samples revealed the presence of other undeclared adulterants. In some cases, the tentative identification of some analytes could be predicted from the fragmentation pattern.
The authors point out that identification of analytes is superior and faster than immunoassays or optical spectroscopy.
Reference
- Guo, B.; Wang, M. et al. Wide-scope screening of illegal adulterants in dietary and herbal supplements via rapid polarity-switching and multistage accurate mass confirmation using an LC-IT/TOF hybrid instrument. J. Agricultural and Food Chem. 2015, 63(31), 6954–67.
Robert L. Stevenson, Ph.D., is Editor Emeritus, American Laboratory/Labcompare; e-mail: [email protected].