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Objective: A sensitive and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was successfully applied to the determination of 10 alkaloids in beagle dog plasma following a single oral dose of Xiatianwu capsules and enteric-coated capsules, with theophylline serving as the internal standard (IS)., Methods: Plasma samples were preprocessed using liquid-liquid extraction (LLE) with ethyl acetate ahead to separation using a gradient elution procedure on a Waters ACQUITY UPLC HSS T3 column (1.8 μm, 100 × 2.1 mm). The mobile phase was composed of 0.1% formic acid solution and acetonitrile at the flow rate of 0.3 ml/min. Multiple reaction monitoring (MRM) was used to determine the analytes in the positive ion mode., Results: The calibration curves for 10 analytes demonstrated a high degree of linearity (r ≥ 0.9920). The lower limit of quantification (LLOQ) values for 10 alkaloids were all more than 1.074 ng/ml, and matrix effects varied from 94.25% to 106.15%. The mean extraction recovery of quality control samples at low (LQC), medium (MQC) and high (HQC) concentrations, as well as IS, was all more than 76.60%. The intra-day and inter-day precision (RSD) also satisfied the requirement. Simultaneously, the variation of assay accuracies (RE) was between 13.05% and 9.38%., Conclusion: The test was validated in accordance with regulatory bioanalytical guidelines and was found to be suitable for use in a pharmacokinetic investigation of these compounds in beagle dogs after oral administration of Xiatianwu general capsules and enteric-coated capsules. The C max of 10 alkaloids ranged from 52.61 to 192.46 ng/ml after oral administration of Xiatianwu capsules, and from 67.50 to 247.36 ng/ml. The T max was between 0.59 and 1.33 h of Xiatianwu capsules, and between 1.08 and 2.00 h of enteric-coated capsules. The t 1/2 ranged from 3.18 to 7.47 h of general capsules, and from 6.01 to 11.36 h. AUC 0-t ranged from 181.06 to 722.74 ng·h/ml of Xiatianwu capsules, and from 275.03 to 884.17 ng·h/ml of enteric-coated capsules. The C max of enteric-coated capsules were significantly increased except for tetrahydropalmatine and berberine. T max of general capsules were less than 1 h, and of enteric-coated capsules were less than 2 h. The t 1/2 of dehydrocorydaline, palmatine, tetrahydrojatrorrhizine, jatrorrhizine and coptisine in enteric-coated capsules was longer than that in ordinary capsule. The AUC 0-t and AUC 0-∞ of bicuculline, dehydrocorydaline, protopine, magnoflorine, tetrahydrojatrorrhizine, jatrorrhizine, berberine and coptisine were all significantly higher in enteric-coated capsules., (© 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Ethnopharmacological Relevance: Coptidis rhizoma (CR) is the dried rhizome of the ranunculaceous plant CR. For decades in China, this plant has been used to treat hypertension, hyperlipidemia, and chronic diarrhea and has been officially included in the Chinese Pharmacopoeia. The present paper presents a review of the pharmacokinetics of CR., Aim of the Study: The pharmacokinetic studies and differences of 10 alkaloids among Coptis deltoidea C. Y. cheng et Hsiao, Coptis chinensis Franch and Coptis teeta Wall. Are seldom reported. This study is the first to determine corydaline, dehydrocorydaline, tetrahydropalmatine, palmatine, magnoflorine, jatrorrhizine, berberine, worenine, berberrubine, and coptisine, which adopted an ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, simultaneously., Materials and Methods: Chromatographic separation was performed within 8 min by using an Agilent SB-C 18 column (150 mm × 2.1 mm, 1.8 μm) with gradient mobile phase consisting of 0.3% acetic acid water (v/v) and acetonitrile at a flow rate of 0.3 mL/min. Multiple reaction monitoring mode was used to detect the tandem mass spectrum in the positive ionization mode by electrospray ionization source., Results: The method was fully validated to be linear over a wide concentration (r > 0.9916), and the linear concentration range was 0.195-2260 ng/mL. Intra- and interday precisions were below 14.19% and 18.56% for the 10 analytes, respectively. The accuracy ranged from -9.30% to 6.31%. The extraction recovery of the 10 alkaloids and internal standard ranged from 79.76% to 95.37%. Pharmacokinetic comparative study showed that the C max and AUC 0-∞ values of dehydrocorydaline, tetrahydropalmatine, palmatine, magnoflorine, jatrorrhizine, berberine, worenine, berberrubine, and coptisine increased significantly (p < 0.05), which was different for beagles after oral administration. The results can help determine the mechanism of action and guide clinical application of these three extracts., Conclusion: This validated method was successfully applied for the pharmacokinetics study of beagle plasma after oral administration of three CR extract types., (Copyright © 2019. Published by Elsevier B.V.)

This study has developed a sensitive and simple ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry method for the simultaneous determination of corydaline, dehydrocorydaline, tetrahydropalmatine, protopine, palmatine, tetrahydroberberine, columbamine, berberine, coptisine and berberrubine in beagle dog plasma after the oral administration of the Corydalis yanhusuo W.T. Wang and Yuanhuzhitong tablets. Chromatographic separation was achieved on an Agilent Eclipse Plus C18 RRHD column (1.8 µm, 50 × 2.1 mm) using a gradient elution program with a mobile phase consisting of acetonitrile and water containing 0.1% formic acid at a flow rate of 0.3 mL/min. A tandem mass spectrometric detection was conducted by multiple reaction monitoring (MRM) mode via an electrospray ionization source in the positive mode. The calibration curves of all analytes showed good linear ( r ² > 0.9800). The intra-day and inter-day precisions were less than 15% and the accuracies were within ±15%. The extraction recoveries conformed to the acceptable range. And there was no interference of endogenous substances in the sensitive assay method. All analytes were proven to be stable during sample storage and analysis procedures. The pharmacokinetic study indicated that the Yuanhuzhitong tablets could get a better absorption than Corydalis yanhusuo W.T. Wang.

Objective: To study the protective effects of Yishen Ruanjian Power (YRP) on renal interstitial fibrosis in rats with chronic aristolochic acid induced nephropathy (CAAN)., Methods: Eighteen male SD rats were divided into 3 groups, 6 in each group. Water solution of Caulis Aristolochia Manshuriensis (CAM) Liquid Extract were given to the mice in the model group by gastrogavage to make CAAN animal model. For those in the TCM group, decocted water solution of YRP was given by gastrogavage after the mice being modeled with the above-mentioned method. Tap water was given by gastrogavage to the mice in the control group. Body weight, 24-hr urinary protein excretion and beta2 microglobulin (beta2-MG), and serum creatinine (r) were determined at the end of the 1st, 4th, 8th, 12th and 16th week. At the end of the 16th week, the rats were sacrificed and the pathological figure of their kidneys were observed by Masson staining. Transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and type I collagen (Col I ) in kidney tissue were determined by RT-PCR and immunohistochemical method, respectively., Results: At end of the 1st week, urinary protein excretion, urinary beta2-MG and SCr in the model group were significantly increased to the levels higher than those in the control group (P < 0.01 or 0.05). Relative area of interstitial fibrosis was significantly enlarged in the model group at the end of the 16th week (P<0.01), and at the same time, the mRNA and protein expression of TCF-beta1, CTGF, PAI-1, TIMP-1 and Col I in kidney tissue were significant up-regulated (P<0.01). After intervention with YRP, the above-mentioned up-regulated parameters, except 24-hr urinary protein excretion, were all significantly inhibited (P <0.01 or 0.05)., Conclusion: YRP could inhibit the accumulation of extracellular matrix in renal interstitial tissue, so as to alleviate the renal interstitial fibrosis and improve the renal function.