1,5-Dimethylhexylamine (octodrine) in sports and weight loss supplements: Natural constituent or synthetic chemical?

Authors: WANG, MEI - University Of Mississippi; HAIDER, SAQLAIN - University Of Mississippi; CHITTIBOYINA, AMAR - University Of Mississippi; PARCHER, JON - University Of Mississippi; KHAN, IKHLAS - University Of Mississippi

Submitted to: Journal of Pharmaceutical and Biomedical Analysis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/3/2018
Publication Date: 2/8/2018
Citation: Wang, M., Haider, S., Chittiboyina, A.G., Parcher, J.F., Khan, I.A. 2018. 1,5-Dimethylhexylamine (octodrine) in sports and weight loss supplements: Natural constituent or synthetic chemical? Journal of Pharmaceutical and Biomedical Analysis. 152:298-305. https://doi.org/10.1016/j.jpba.2018.02.008.
DOI: https://doi.org/10.1016/j.jpba.2018.02.008

Interpretive Summary: Octodrine is an ingredient in newly appeared sports and weight loss supplements with its ‘natural’ origin being cited from Aconitum or Kigelia plants. This simulant is structurally similar to 1,3-dimethylamylamine, which was banned by the US Food and Drug Administration from the dietary supplements due to the safety concerns. The manuscript presents a detailed discussion to determine whether octodrine is from natural or synthetic source. Two analytical methods, conventional and chiral GC/MS, were developed. The quantity of octodrine present in the supplements was determined by conventional GC/MS, and was more than three times the largest pharmaceutical dose. Enantiomeric distribution determined by chiral GC/MS suggested the synthetic origin of octodrine in the supplements. In addition, identification of synthetic artifacts in the supplements from synthesis of octodrine further confirmed the synthetic origin of octodrine detected in supplements. It was concluded that adulteration by illegal addition of pharmaceutical substances or their analogs poses a significant issue for consumers and regulatory agencies.

Technical Abstract: In the past years, there has been a mounting trend toward the addition of sympathomimetic stimulants in sports and weight loss supplements sold in the US and claimed to be from natural constituents. The latest among those pharmaceutical stimulants is 1,5-dimethylhexylamine (1,5-DMHA or octodrine), an ingredient in newly introduced sports and weight loss supplements with its ‘natural’ origin being cited from Aconitum or Kigelia plants. In order to validate the natural existence of 1,5-DMHA, two GC/MS methods were developed. One method involved using thick film megabore capillary columns to analyze the underivatized 1,5-DMHA. The second method was to determine enantiomeric distribution of 1,5- DMHA. Fifteen Aconitum or Kigelia plant samples originating from various locations were analyzed, and none of them contained 1,5-DMHA within the limit of detection (25 ng/mL) of the method. In contrast, although 1,5-DMHA was listed on the labels or website for all the 13 dietary supplements, only four products were found to contain this compound, with the highest quantity being reported as 112 mg per serving size. This is equivalent to more than three times the highest pharmaceutical dose established in Europe. The enantiomeric ratios of 1,5-DMHA in these products were determined to be between 0.9–1.0 (expressed as peak area ratio of one enantiomer over another), suggesting racemic nature. Interestingly, two byproducts from 1,5-DMHA synthesis were identified in commercial supplements containing 1,5- DMHA, indicating that 1,5-DMHA indeed originated from a poor quality source. Overall, the significant amount of 1,5-DMHA observed in the supplements, the enantiomeric distribution and the presence of the synthetic byproducts all suggested the synthetic origin of 1,5-DMHA in the commercial products.