Kratom, Mitragyna speciosa Korth., is being widely consumed in the United States for pain management and the reduction of opioid withdrawal symptoms. The central nervous system (CNS) active alkaloids of kratom, including mitragynine, 7-hydroxymitragynine, and numerous additional compounds, are believed to derive their effects through opioid receptor activity. There is no literature describing the systemic exposure of many of these alkaloids after the consumption of kratom. Therefore, we have developed and validated a bioanalytical method for the simultaneous quantitation of 11 kratom alkaloids (mitragynine, 7-hydroxymitragynine, corynantheidine, speciogynine, speciociliatine, paynantheine, corynoxine, corynoxine-B, mitraphylline, ajmalicine, and isospeciofoline) in rat plasma. The validated method was used to analyze oral pharmacokinetic study samples of lyophilized kratom tea (LKT) and a marketed product, OPMS liquid shot, in rats. Among the 11 alkaloids, only mitragynine, 7-hydroxymitragynine, speciociliatine, and corynantheidine showed systemic exposure 8 h postdose, and the dose-normalized systemic exposure of these four alkaloids was higher (1.6–2.4-fold) following the administration of the commercial OPMS liquid. Paynantheine and speciogynine levels were quantifiable up to 1 h postdose, whereas none of the other alkaloids were detected. In summary, the method was successfully applied to quantify the exposure of individual kratom alkaloids after an oral dose of traditional or commercial products. This information will contribute to understanding the role of each alkaloid in the overall pharmacology of kratom and elucidating the pharmacokinetic differences between traditional and commercial kratom products.

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Background In 2018, the Farm Bill mandated the United States Department of Agriculture to develop regulations governing the cultivation, processing, and marketing of industrial hemp. Industrial hemp is defined as Cannabis sativa L. with a total Δ-9-tetrahydrocannabinol (Δ-9-THC) content ≤0.3%. Therefore, for hemp to become an agricultural commodity, it is important to regulate production by developing standard methods for sampling and testing of the plant material. Methods An ultra-performance liquid chromatography-tandem mass spectrometry analytical method for the quantification of twelve cannabinoids was developed. The method was applied to a regulatory sampling trial of three hemp varieties cultivated for cannabidiol (CBD) production. Two samples were taken from 28 plants with one sample being flower only while the other was a composite sample that included flowers, leaves, and stems. Results The assay method was validated for specificity, range, repeatability, reproducibility, and recovery in accordance with all applicable standards for analytical methods. The results of the regulatory study indicated a significant decrease in the concentration of total Δ-9-THC and total CBD of 0.09% and 1.32%, respectively, between a flower only and a composite sample. Conclusions There are many factors that may influence reported total Δ-9-THC content in industrial hemp. A robust analytical method was developed to analyze hemp samples in a trial regulatory study. The results indicate that the way hemp is sampled and analyzed may influence the legality of a crop, which could have negative economic and legal consequences.

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