Mislabeling and Status of Semisynthetic Kratom-Derived Products in the US Market.

Kratom (Mitragyna speciosa), a plant native to Southeast Asia, has traditionally been used for stimulant and analgesic effects, yet its safety profile remains poorly understood given its complex polypharmacology and rapidly evolving commercial formulations. It contains a wide variety of indole alkaloids, with mitragynine (MTG) as the major constituent and most abundant psychoactive alkaloid. There has been a rapid growth of the kratom market, accompanied by a marked increase in kratom-related exposures, hospitalizations, and deaths in the United States, coinciding with the introduction of kratom-derived semisynthetic products, as reflected in rising poison control center calls reported by the US Centers for Disease Control and Prevention (CDC). In this context, the present study aims to analyze commercially available kratom products collected from multiple locations using a UPLC-MS/MS method, with the objective of characterizing their alkaloid profiles and assessing labeling accuracy and product integrity. Results demonstrated substantial variability in alkaloid composition across tablets, films, and liquid shots, with frequent inconsistencies between labeled and actual contents. Products often contained additional unreported alkaloids or lacked those listed on the label; however, most still included pharmacologically and toxicologically active compounds, such as 7-hydroxymitragynine (7-HMG) and 3-dehydromitragynine (3DMTG), respectively. Overall, these findings indicate inconsistent manufacturing practices, labeling inaccuracies, and potential adulteration, along with the risk of exposure to highly potent mu-opioid receptor (MOR) agonists. Collectively, this highlights the need for improved regulatory oversight and strengthened post-marketing surveillance, including real-time poison control center data, to ensure consumer safety.