Inhibitory effects of Kratom constituents, mitragynine and 7-hydroxymitragynine, on 4-methylumbelliferone glucuronidation by human UDP-glucuronosyltransferases

Article

作者: Uchaipichat, Verawan

As Kratom use increases, concerns about potential herb-drug interactions with liver enzymes, particularly UDP-glucuronosyltransferases (UGTs), have emerged. This study investigated the inhibitory effects of Kratom leaf constituents, mitragynine and 7-hydroxymitragynine, on 4-methylumbelliferone (4MU) glucuronidation by a panel of recombinant human UGT enzymes, including UGT1A1, UGT1A3, UGT1A6, UGT1A9, UGT2B7, and UGT2B15. The degree of inhibition exhibited by mitragynine and 7-hydroxymitragynine on UGTs varied. Mitragynine exhibited the highest inhibitory potency on UGT1A3 with an IC₅₀ value of 72 µM. Moderate inhibition potency of mitragynine were observed for UGT1A6, UGT1A9 and UGT2B15, with IC₅₀ value of 121, 131, and 152 µM, respectively, whereas the inhibition on UGT1A1 and UGT2B7 was low (IC₅₀ > 200 µM). 7-Hydroxymitragynine exhibited the highest inhibitory potency on UGT1A9, with IC₅₀ value of 51 µM, while moderate potency was observed for UGT1A1 and UGT1A3, with IC₅₀ value of 196 and 141 µM, respectively. The inhibitory potency of 7-hydroxymitragynine on UGT2B15 was low (IC₅₀ > 200 µM), while negligible effects were observed for UGT1A6 and UGT2B7. Kinetic inhibition study revealed that mitragynine noncompetitively inhibited UGT1A3 (K_i = 45 µM) and competitively inhibited UGT1A9 (K_i = 114 µM), while 7-hydroxymitragynine competitively inhibited UGT1A3 (K_i = 33 µM) and noncompetitively inhibited UGT1A9 (K_i = 29 µM). The experimental K_i values found here are relatively high compared to the maximum plasma concentrations of mitragynine and 7-hydroxymitragynine reported in humans, suggesting an unlikely potential for herb-drug interactions via UGT inhibition.

2024-09-01·ANALYTICA CHIMICA ACTA

Development of a CZE-MS/MS method with dynamic pH junction sample pretreatment for analysis of kratom psychoactive alkaloids in urine

Article

作者: Horniakova, Andrea ; Piestansky, Juraj ; Mikus, Peter

BACKGROUND:

Kratom is a herbal substance belonging to the group of new psychoactive substances. It contains psychoactive indole alkaloids mitragynine and 7-hydroxymitragynine. At low doses, they act as psychostimulants and at higher doses they mediate an opioid-like effect. The increasing misuse of kratom requires the development of analytical methods that will accurately and reliably identify and quantify its psychoactive alkaloids in biological samples. Therefore, the development of effective, precise, and reliable green analytical methods that are easy to implement in practice is of great importance. On-line combination of capillary zone electrophoresis with tandem mass spectrometry (CZE-MS/MS) seems to be a promising solution.

RESULTS:

We present a novel green approach based on capillary zone electrophoresis - tandem mass spectrometry (CZE-MS/MS) method with on-line dynamic pH junction sample pretreatment to identify and determine mitragynine and 7-hydroxymitragynine in urine samples. The separation was performed in a background electrolyte composed of 100 mM formic acid (pH 2.39). The dynamic pH junction was ensured by injection of a short plug of 12.5 % NH₄OH before the sample. Under optimal conditions, the developed method was validated and parameters such as linearity (r² > 0.99), precision (2.2-8.7 %), accuracy (89.2-102.5 %) or stability of the sample (86.6-114.7 %) met the defined FDA guideline criteria (%RSD and %RE values where within ±15 %). Introduction of a simple in-capillary preconcentration strategy based on dynamic pH junction enabled significant improvement in analytical signal intensity and also the applicability of the method. Applying the presented approach, high sensitivity was achieved as indicated by limit of detection values, which were 0.5 ng mL^-1 and 2 ng mL^-1 for mitragynine and 7-hydroxymitragynine, respectively. Greenness of the proposed approach was confirmed by the AGREE metrics (score 0.63). The application potential of the developed method was successfully verified using blinded urine model samples.

SIGNIFICANCE:

For the first time a fully validated CZE-MS/MS method for kratom alkaloids determination was introduced. The presented novel method is a cheaper and more ecological alternative to conventionally used chromatographic techniques what was clearly confirmed by its greenness evaluation and comparison with previously published liquid chromatography (LC) approaches. In-capillary sample pretreatment (dynamic pH junction) has been demonstrated to be an effective and fast tool in bioanalysis, minimizing the number of pretreatment steps and the manipulation with the sample. Moreover, LOD values comparable to those obtained by LC methods were recorded. High potential for the implementation of this approach into the toxicology environment in the near future is expected.

2023-11-01·Journal of analytical toxicology

Mitragynine in the Orange County DUID population

Article

作者: Kedzierski, Nancy ; Mata, Dani

Abstract:

In recent years, mitragynine has been consistently detected in driving under the influence of drug (DUID) cases. In this paper, we evaluate 3 years (2017–2019) worth of DUID data from arrested drivers in Orange County, CA, USA. From the 25,398 DUID cases received in those 3 years, there were 60 (0.24%) cases with detectable concentrations, >10 ng/mL, of mitragynine. The majority of drivers were male (90%) and were stopped during the week (81%), considered Monday 0000 to Friday 1159. The concentration range for all mitragynine cases was 10.5–960 ng/mL, with a mean of 109 ng/mL and a median of 58 ng/mL. Forty four of the 60 cases were also screened for 7-hydroxymitragynine, and 27 (63%) were positive. The police reports and drug recognition expert evaluations were collected and evaluated. No case contained solely mitragynine, and the most common drugs detected in combination were central nervous system depressants (ethanol, followed by benzodiazepines), stimulants (methamphetamine and cocaine) and opioids (fentanyl and indication of heroin). Two cases containing only one other psychoactive substance are discussed more thoroughly to attempt to identify the contributions of mitragynine to driving impairment. Collected demographic, toxicological and field observations are presented for all cases.

项与 7-OH-MTG 相关的新闻（医药）

2025-02-12

·PRNewswire

SABER Issues Warning on the Public Health Risks of Synthetic 7-OH

CLEVELAND, Feb. 12, 2025 /PRNewswire/ -- The Scientific Association for Botanical Education and Research (SABER) is raising alarms about the rising public health threat posed by products labelled as 7-hydroxymitragynine (7-OH), a dangerous synthetically produced product often falsely marketed as a kratom leaf extract. Unlike kratom leaves, which have been consumed traditionally for its mild energy and analgesic properties, these lab produced products contain predominately synthetic 7-OH which poses risks of addiction, toxicity, and misuse. "Synthetic 7-OH is not kratom—it is a highly potent, unregulated chemical," says Professor Paula Brown of the BC Institute of Technology. "Consumers have a right to transparency, yet these products are often mislabeled and marketed deceptively as natural extracts, without proper quality and safety testing, they carry a significant risk of causing harm." Key Concerns Highlighted by SABER Potency and Abuse Potential: Synthetic 7-OH is up to 30 times more potent than morphine at opioid receptors, significantly increasing the risk of dependence and overdose. Masquerading as Natural Products: These synthetic products are often deceptively marketed as "natural kratom extracts," misleading consumers who believe they are purchasing a safer, plant-based product. Health Risks: Due to the lack of clinical safety data, synthetic 7-OH products pose severe risks, including respiratory depression, toxicity, and addiction. Regulatory Non-Compliance: Synthetic 7-OH fails to meet FDA definitions of a food or dietary ingredient and is considered an unapproved drug. Many states, including Arizona, Oklahoma, Texas, and Utah, have enacted bans on synthetic 7-OH exceeding 2% of total alkaloid content in products. A Call for Consumer and Regulatory Action SABER urges policymakers to enforce stricter regulations on synthetic 7-OH products and calls for penalties against unscrupulous manufacturers that mislead consumers. Comprehensive legislation aligned with Kratom Consumer Protection Acts is needed to protect the public and preserve access to safe, natural kratom products. It is imperative swift action is taken to close regulatory loopholes that allow dangerous synthetic 7-OH products to infiltrate the market. Consumers, health professionals, and legislators must unite to demand accountability and ensure safety. About SABER The Scientific Association for Botanical Education and Research (SABER) is dedicated to advancing scientific understanding, education, and regulation of botanicals. Through rigorous research, advocacy, and education, SABER promotes safe and informed use of plant-based products. For more information or media inquiries, please contact [email protected] Website: SOURCE The Scientific Association for Botanical Education and Research (SABER) WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

100 项与 7-OH-MTG 相关的药物交易

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