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Context: Tadehaginoside, an active ingredient isolated from Tadehagi triquetrum (Linn.) Ohashi (Leguminosae), exhibited various biological activities. However, the pharmacokinetics and tissue distribution which affect tadehaginoside's therapeutic actions and application remain elusive., Objective: To clarify the metabolism of tadehaginoside in vivo ., Materials and Methods: The pharmacokinetics and tissue distribution of tadehaginoside and its metabolite p -hydroxycinnamic acid (HYD) were investigated using LC-MS/MS. Pharmacokinetic parameters were determined in 10 Sprague-Dawley rats divided into two groups, the intravenous group (5 mg/kg) and the oral group (25 mg/kg). For the tissue-distribution study, 20 rats were intravenously given tadehaginoside (5 mg/kg) before the experiment ( n  = 4). Biological samples were collected before drug administration (control group) and after drug administration., Results: The linearity, accuracy, precision, stability, recovery and matrix effect of the method were well-validated and the results satisfied the requirements of biological sample measurement. Treatment with tadehaginoside via intragastric and intravenous administration, the calculated C max in rats was 6.01 ± 2.14 ng/mL and 109.77 ± 4.29 ng/mL, and T max was 0.025 ± 0.08 h and 0.08 h, respectively. The results indicated that the quick absorption of tadehaginoside was observed following intravenous administration, and tadehaginoside in plasma of rats with intragastric administration showed relatively low concentration may be due to the formation of its metabolite. Tissue-distribution study indicated that kidney and spleen were the major distribution organs for tadehaginoside in rats and there was no long-term accumulation in most tissues., Discussion and Conclusion: These results could provide clues for exploring the bioactivity of tadehaginoside based on its pharmacokinetic characteristics.

This study aimed to develop a rapid, sensitive, and specific LC-tandem mass spectrometry method for the determination of nootkatone in rat plasma. α-Cyperone was chosen as the internal standard (IS). The plasma was processed using a one-step acetonitrile protein precipitation method. Chromatographic separation of nootkatone was achieved on a Phenomenex Kinetex XB-C18 column (2.10 × 50 mm, 2.6 μm) at 35°C with a mobile phase consisting of acetonitrile and water under a gradient elution at a flow rate of 0.35 mL/min. An electrospray ionization source was applied and operated in positive ion and multiple reaction monitoring modes. Nootkatone and IS were quantified using the transitions of m/z 219.200 → 163.110 and m/z 219.200 → 111.000, respectively. The calibration curves were linear over the range of 10-2000 ng/mL (r = 0.9943). The lower limit of quantification was 10 ng/mL. The intra- and inter-day precision (relative standard deviation) ranged from 2.56% to 8.41%, with the accuracy values ranging from 98.9% to 99.17% for four different concentration levels. The matrix effect and extraction recovery were within acceptable limits. The validated method was successfully applied to the pharmacokinetic study of nootkatone in rats after oral and intravenous administration at three dosages. The main pharmacokinetic parameters were calculated, showing low bioavailability of nootkatone., (© 2021 John Wiley & Sons, Ltd.)

Context: Laurolitsine is an aporphine alkaloid and exhibits potent antihyperglycemic and antihyperlipidemic effects in ob/ob mice., Objective: To investigate the pharmacokinetics, tissue distribution and excretion of laurolitsine., Materials and Methods: A LC-MS/MS method was established and validated to determine laurolitsine concentrations in the biological matrix of rats (plasma, tissue homogenate, urine and faeces). 10 Sprague-Dawley (SD) rats were used for plasma exposure study: 5 rats were injected with 2.0 mg/kg of laurolitsine via the tail vein, and the other 5 rats were administered laurolitsine (10.0 mg/kg) by gavage. 25 SD rats used for tissue distribution study and 5 SD rats for urine and faeces excretion study: rats administered laurolitsine (10.0 mg/kg) by gavage. After administered, serial blood, tissue, urine and faeces were collected. Analytical quantification was performed by a previous LC-MS/MS method. The pharmacokinetics, bioavailability, tissue distribution and excretion of laurolitsine were described., Results: The pharmacokinetic parameters of oral and intravenous administration with T max were 0.47 and 0.083 h, t 1/2 were 3.73 and 1.67 h, respectively. Oral bioavailability was as low as 18.17%. Laurolitsine was found at a high concentration in the gastrointestinal tract, liver, lungs and kidneys (26 015.33, 905.12, 442.32 and 214.99 ng/g at 0.5 h, respectively) and low excretion to parent laurolitsine in urine and faeces (0.03 and 1.20% in 36 h, respectively)., Conclusions: This study established a simple, rapid and accurate LC-MS/MS method to determine laurolitsine in different rat samples and successful application in a pharmacokinetic study.

The aim of the present study was to develop a rapid, specific and sensitive LC-MS/MS method for the determination of DPHB [7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-4-hepten-3-one] in rat plasma using yakuchinone A as an internal standard (IS). n-Hexane was used for the extraction of DPHB from rat plasma. Chromatographic separation of DPHB was achieved using a Kinetex XB-C 18 column (2.10 × 50 mm, 2.6 μm) at 40°C. The mobile phase consisted of water (containing 0.1‰ formic acid, A) and acetonitrile (containing 0.1‰ formic acid, B) under a gradient elution at a flow rate of 0.3 mL min -1 . Positive electrospray ionization and multiple reaction monitoring mode were used for detection. The selected precursor ion to product ion pairs, m/z 311.3 → 137.0 for DPHB and m/z 313.1 → 137.0 for yakuchinone A, were monitored. Good linearity was observed over the concentration range from 2 to 2000 ng mL -1 (r = 0.9969). The recovery efficiency of DPHB from rat plasma was 54.8-69.7%, while the matrix effect ranged from 99.7 to 113%. Intra- and inter-day precision and accuracy values were within ±15% at three different quality control concentration levels. This validated method was successfully applied to pharmacokinetic studies in rats after a single p.o. or i.v. dose of DPHB solution. The route of administration significantly influenced systemic exposure to DPHB, and low bioavailability of DPHB was observed. The method developed here will be further improved and used in future pharmacokinetic studies., (© 2018 John Wiley & Sons, Ltd.)

In this study, a simple, sensitive, and rapid analytical method was developed by ultra-performance liquid chromatography (UPLC) coupled with tandem quadrupole mass spectrometry (MS) for the determination of nootkatone in normal and chronic kidney disease (CKD) rat plasma using clarithromycin as internal standard. After sample preparation by simple liquid–liquid extraction, chromatography was performed on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 mm particle size) using gradient elution with the mobile phase composed of acetonitrile and water acidified with 0.1% (v/v) formic acid. Detection was achieved by electrospray ionisation MS under the multiple selective reaction monitoring mode. The linear range was 0.01‒500 ng/mL with the square regression coefficient (r) of 0.9975. The lower limit of quantification was 0.01 ng/mL. The intra- and inter-day precision was under 5% and the stability accuracy was between 3.6 and 7.0%. The average recoveries from spiked plasma samples were >83% and matrix effect was over 81%. The developed method was successfully applied to the pharmacokinetic study of nootkatone in normal and CKD rats after an oral administration of 50 mg/kg nootkaone. The results showed the cmax and area under curve of nootkaone were greatly decreased, meanwhile Vd/F and t1/2 were markedly increased in CKD rats. The pharmacokinetic characteristics of nootkatone in rats were significantly altered in CKD rats. [ABSTRACT FROM AUTHOR]

Highlights: [•] Alpinia oxyphylla (Yizhi) capsularfruits are commonly used in traditional medicine. [•] The chemicals and their metabolites in rat plasma were identified using LC–MS/MS with MRM mode. [•] Yizhi flavonoids and diarylheptanoids formed mainly monoglucuronide metabolites. [•] Metabolic reduction of Yizhi diarylheptanoids occurred in rats. [Copyright &y& Elsevier]