title: Understanding the physicochemical properties of mitragynine, a principal alkaloid of Mitragyna speciosa, for preclinical evaluation.
abstract: Varied pharmacological responses have been reported for mitragynine in the literature, but no supportive scientific explanations have been given for this. These studies have been undertaken without a sufficient understanding of the physicochemical properties of mitragynine. In this work a UV spectrophotometer approach and HPLC-UV method were employed to ascertain the physicochemical properties of mitragynine. The pKa of mitragynine measured by conventional UV (8.11 ± 0.11) was in agreement with the microplate reader determination (8.08 ± 0.04). Mitragynine is a lipophilic alkaloid, as indicated by a logP value of 1.73. Mitragynine had poor solubility in water and basic media, and conversely in acidic environments, but it is acid labile. In an in vitro dissolution the total drug release was higher for the simulated gastric fluid but was prolonged and incomplete for the simulated intestinal fluid. The hydrophobicity, poor water solubility, high variability of drug release in simulated biological fluids and acid degradable characteristics of mitragynine probably explain the large variability of its pharmacological responses reported in the literature. The determined physicochemical properties of mitragynine will provide a basis for developing a suitable formulation to further improve its solubility, stability and oral absorption for better assessment of this compound in preclinical studies.
authors: Centre for Drug Research, Universiti Sains Malaysia, Penang 11800, Malaysia.
authors: Surash
authors: S
authors: Ramanathan
authors: Centre for Drug Research, Universiti Sains Malaysia, Penang 11800, Malaysia. suhanya@hotmail.com.
authors: Suhanya
authors: S
authors: Parthasarathy
authors: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
authors: Vikneswaran
authors: V
authors: Murugaiyah
authors: Advanced Medical & Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Penang 13200, Malaysia.
authors: Enrico
authors: E
authors: Magosso
authors: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang 11800, Malaysia.
authors: Soo Choon
authors: SC
authors: Tan
authors: Centre for Drug Research, Universiti Sains Malaysia, Penang 11800, Malaysia.
authors: Sharif Mahsufi
authors: SM
authors: Mansor
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004353:Drug Evaluation, Preclinical; D032065:Mitragyna / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D046948:Secologanin Tryptamine Alkaloids / Q000737:chemistry* / Q000302:isolation & purification*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
chemical_list: D046948:Secologanin Tryptamine Alkaloids; C001801:mitragynine