Simultaneous quantification of ten key Kratom alkaloids in <i>Mitragyna speciosa</i> leaf extracts and commercial products by ultra‐performance liquid chromatography−tandem mass spectrometry

Sharma, Abhisheak; Kamble, Shyam H.; León, Francisco; Chear, Nelson Jeng Yeou; King, Tamara I.; Berthold, Erin C.; Ramanathan, Surash; McCurdy, Christopher R.; Avery, Bonnie A.

doi:10.1002/dta.2604

Cited by 79 publications

(91 citation statements)

References 25 publications

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Section: Reagents and Chemicalsmentioning

confidence: 99%

“…Mitragynine (as mitragynine sulfate salt; purity ≥ 98 %) was isolated and purified from a kratom alkaloid-enriched extract (Choice Organics) as described in our earlier published papers [27,43]. 7-Hydroxymitragynine (purity ≥ 98 %) was obtained through mitragynine semi-synthesis as previously reported [43]. Purity and structural characterization of mitragynine, mitragynine sulfate, and 7-hydroxymitragynine were established by proton nuclear magnetic resonance spectroscopy ( 1 H NMR), carbon ( 13 C) NMR, ▶ Table 4 Pharmacokinetic parameters of mitragynine after oral (5 mg/kg) and intravenous (0.1 mg/kg) administration in female beagle dogs.…”

Section: Reagents and Chemicalsmentioning

confidence: 99%

“…a N = 5, values are the mean ± SEM. Abbreviations: AUC = area under the plasma concentration-time curve, C max = plasma peak concentration, T max = time to reach C max 2D NMR, ultrahigh-performance liquid chromatography-photodiode array detection (UHPLC-PDA), and liquid chromatography high-resolution quadrupole time of flight mass spectrometry (LC-Q-TOF) [43]. LC-MS grade acetonitrile, methanol, formic acid, and water were procured from Fisher Scientific.…”

Section: Parameter 7-hydroxymitragyninementioning

confidence: 99%

“…The composition of component A in the mobile phase was further increased to 80 % by 3.6 min, and was maintained until 5.5 min. Compositions and volumes of weak and strong needle washes were implemented from the method of Sharma et al [43]. A simple and fast protein precipitation method was used for the removal of endogenous substances and extraction of mitragynine and 7-hydroxymitragynine from dog plasma.…”

Section: Parameter 7-hydroxymitragyninementioning

confidence: 99%

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Pharmacokinetics and Safety of Mitragynine in Beagle Dogs

et al. 2020

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Mitragynine is the most abundant psychoactive alkaloid derived from the leaves of Mitragyna speciosa (kratom), a tropical plant indigenous to regions of Southeast Asia. Mitragynine displays a moderate affinity to opioid receptors, and kratom is often self-prescribed to treat pain and/or opioid addiction. The purpose of this study was to investigate the safety and pharmacokinetic properties of mitragynine in the dog. Single dose oral (5 mg/kg) and intravenous (0.1 mg/kg) pharmacokinetic studies of mitragynine were performed in female beagle dogs. The plasma concentrations of mitragynine were measured using ultra-performance liquid chromatography coupled with a tandem mass spectrometer, and the pharmacokinetic properties were analyzed using non-compartmental analysis. Following intravenous administration, mitragynine showed a large volume of distribution (Vd, 6.3 ± 0.6 L/kg) and high clearance (Cl, 1.8 ± 0.4 L/h/kg). Following oral mitragynine dosing, first peak plasma (Cmax, 278.0 ± 47.4 ng/mL) concentrations were observed within 0.5 h. A potent mu-opioid receptor agonist and active metabolite of mitragynine, 7-hydroxymitragynine, was also observed with a Cmax of 31.5 ± 3.3 ng/mL and a Tmax of 1.7 ± 0.6 h in orally dosed dogs while its plasma concentrations were below the lower limit of quantification (1 ng/mL) for the intravenous study. The absolute oral bioavailability of mitragynine was 69.6%. Administration of mitragynine was well tolerated, although mild sedation and anxiolytic effects were observed. These results provide the first detailed pharmacokinetic information for mitragynine in a non-rodent species (the dog) and therefore also provide significant information for allometric scaling and dose predictions when designing clinical studies.

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Section: Reagents and Chemicalsmentioning

confidence: 99%

Section: Reagents and Chemicalsmentioning

confidence: 99%

Section: Parameter 7-hydroxymitragyninementioning

confidence: 99%

Section: Parameter 7-hydroxymitragyninementioning

confidence: 99%

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Pharmacokinetics and Safety of Mitragynine in Beagle Dogs

et al. 2020

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“…Indole alkaloids in leaves of Mitragyna speciosa Korth. were measured with buffer system containing ammonium acetate at pH 3.5 [18]. Mobile phase consisting of FA and ACN was employed for alkaloids from seeds of different Ipomoea species and cultivars [19] as well as roots and leaves of seven Rauvolfia species [20].…”

Section: Chromatographic Separation Methodsmentioning

confidence: 99%

Liquid chromatographic separation of alkaloids in herbal medicines: Current status and perspectives

Zhao

Chen

Yu-qian

et al. 2020

J of Separation Science

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Alkaloids are a widespread group of basic compounds in herbal medicines and have attracted great interest due to various pharmaceutical activities and desirable druggability. Their distinctive structures make chromatographic separation fairly difficult. Peak tailing, poor resolution, and inferior column‐to‐column reproducibility are common obstacles to overcome. In order to provide a valuable reference, the methodologies and/or strategies on liquid chromatographic separation of alkaloids in herbal medicines proposed from 2012 to 2019 are thoroughly summarized.

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Preclinical pharmacokinetic studies of villocarine A, an active Uncaria alkaloid

Chiang,

Chear,

Berthold

et al. 2024

Drug Testing and Analysis

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Villocarine A is a bioactive indole alkaloid isolated from the Uncaria genus. It has demonstrated vasorelaxation activity and potential to protect the central nervous system. To identify the pharmacokinetic properties of villocarine A, a series of in vitro and in vivo studies have been performed. Villocarine A was found to be highly permeable (15.6 ± 1.6*10−6 cm/s) across human colorectal adenocarcinoma cell monolayer with high protein binding (>91%) in both rat and human plasma. Hepatic extraction ratio of villocarine A was 0.1 in pooled rat liver and 0.2 in human liver microsomes and was found stable in rat plasma at 37°C. Due to the high permeability and low rate of metabolism properties, villocarine A was initially considered suitable for preclinical development and an ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for quantification (linearity: 1–150 ng/ml) in rat plasma was developed and validated for in vivo studies. Essential pharmacokinetic parameters included the volume of distribution and clearance of villocarine A, which were found to be 100.3 ± 15.6 L/kg and 8.2 ± 1.1 L/h/kg, respectively, after intravenous administration in rats. Following oral dosing, villocarine A exhibited rapid absorption as the maximum plasma concentration (53.2 ± 10.4 ng/ml) occurred at 0.3 ± 0.1 h, post‐dose. The absolute oral bioavailability of villocarine A was 16.8 ± 0.1%. To our knowledge, this was the first pharmacokinetic study of villocarine A, which demonstrated the essential pharmacokinetic properties of villocarine A: large volume distribution, high clearance, and low oral bioavailability in rats.

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Simultaneous quantification of ten key Kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by ultra‐performance liquid chromatography−tandem mass spectrometry

Cited by 79 publications

References 25 publications

Pharmacokinetics and Safety of Mitragynine in Beagle Dogs

Pharmacokinetics and Safety of Mitragynine in Beagle Dogs

Liquid chromatographic separation of alkaloids in herbal medicines: Current status and perspectives

Preclinical pharmacokinetic studies of villocarine A, an active Uncaria alkaloid

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