Development and validation of a high performance liquid chromatography quantification method of levo‐tetrahydropalmatine and its metabolites in plasma and brain tissues: application to a pharmacokinetic study

Abstract

Levo-tetrahydropalmatine (l-THP) is an alkaloid isolated from Chinese medicinal herbs of the Corydalis and Stephania genera. It has been used in China for more than 40 years mainly as an analgesic with sedative/hypnotic effects. Despite its extensive use, its metabolism has not been quantitatively studied, nor there a sensitive reliable bioanalytical method for its quantification simultaneously with its metabolites. As such, the objective of this study was to develop and validate a sensitive and selective HPLC method for simultaneous quantification of l-THP and its desmethyl metabolites l-corydalmine (l-CD) and l-corypalmine (l-CP) in rat plasma and brain tissues. Rat plasma and brain samples were processed by liquid-liquid extraction using ethyl acetate. Chromatographic separation was achieved on a reversed-phase Symmetry® C column (4.6 × 150 mm, 5 μm) at 25°C. The mobile phase consisted of acetonitrile-methanol-10 mm ammonium phosphate (pH 3) (10:30:60, v/v) and was used at a flow rate of 0.8 mL/min. The column eluent was monitored at excitation and emission wavelengths of 230 and 315 nm, respectively. The calibration curves were linear over the concentration range of 1-10,000 ng/mL. The intra- and interday reproducibility studies demonstrated accuracy and precision within the acceptance criteria of bioanalytical guidelines. The validated HPLC method was successfully applied to analyze samples from a pharmacokinetic study of l-THP in rats. Taken together, the developed method can be applied for bioanalysis of l-THP and its metabolites in rodents and potentially can be transferred for bioanalysis of human samples.

A Comprehensive Review on the Chemical Properties, Plant Sources, Pharmacological Activities, Pharmacokinetic and Toxicological Characteristics of Tetrahydropalmatine

“…Multiple demethylations, glucuronic acid and sulfate coupling, and renal excretion of THP in humans are the main drug clearance pathways of THP. THP has four monodesmethyl metabolites: L-isocorypalmine, L-corypalmine, L-tetrahydropalmatrubine, and L-corydalmine ( Abdallah et al, 2017 ). The mean time to peak concentration (T max ) and half-life (T 1/2 ) of THP in rats were 0.44 and 4.49 h, respectively ( Wang W. et al, 2017 ), whereas those of healthy cocaine-using adults were 1.5 and 13.3 h, respectively ( Hassan et al, 2017 ).…”

Development and Validation of a HPLC-ESI-MS/MS Method for Simultaneous Quantification of Fourteen Alkaloids in Mouse Plasma after Oral Administration of the Extract of Corydalis yanhusuo Tuber: Application to Pharmacokinetic Study

“…It is well known that the main active ingredients of the extract of C. yanhusuo are the alkaloids, which possess potent pharmacological effects, such as antinociceptive, antitumor, antibacterial, anti-inflammatory, and anti-depressive activities. For example, tetrahydropalmatine, corydaline, and protopine could enter the central nervous system through the blood-brain barrier, and play the role of analgesic, sedative hypnotic, and anxiolytic effects [ 1 , 2 , 3 , 4 ]. Oxoglaucine, berberrabine, berberine, coptisine, palmatine, columbamine, and jatrorrhizine were reported to have antitumor activity [ 5 , 6 , 7 ], while berberine, palmatine and epiberberine were found to have antibacterial activity [ 8 , 9 ].…”

Peanut Rotation and Flooding Induce Rhizobacteriome Variation With Opposing Influences on the Growth and Medicinal Yield of Corydalis yanhusuo

“…Modern medical research has revealed that the C. yanhusuo extract has significant inhibitory effects upon acetylcholinesterase (AChE) and cancer cell proliferation, as well as beneficial effects for the cardiovascular system (Ling et al, 2006;Xiao et al, 2011;Chen et al, 2016). To date, more than 100 compounds have been isolated and identified from RC, including fatty acids, organic acids, amino acids, sugars, steroids, anthraquinones, volatile compounds, and alkaloids (Hung and Wu, 2016;Abdallah et al, 2017;Hassan et al, 2017). In particular, over 80 types of alkaloids have been isolated and identified (Tian et al, 2020), these being major pharmacologically active compounds for the treatment of blood vessel diseases, tumors, and various pains (Li et al, 2014;Wu et al, 2016).…”