scholarly journals Simultaneous Determination of Bufalin and Its Nine Metabolites in Rat Plasma for Characterization of Metabolic Profiles and Pharmacokinetic Study by LC–MS/MS

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1662
Author(s):  
Wenlong Wei ◽  
Yang Yu ◽  
Xia Wang ◽  
Linhui Yang ◽  
Hang Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Simultaneous Determination ◽  
Pharmacokinetic Study ◽  
Metabolic Pathways ◽  
Multiple Reaction Monitoring ◽  
Rat Plasma ◽  
Limit Of Quantitation

Characterization and determination of metabolites to monitor metabolic pathways play a paramount role in evaluating the efficacy and safety of medicines. However, the separation and quantification of metabolites are rather difficult due to their limited contents in vivo, especially in the case of Chinese medicine, due to its complexity. In this study, an effective and convenient method was developed to simultaneously quantify bufalin and its nine metabolites (semi-quantitation) in rat plasma after an oral administration of 10 mg/kg to rats. The prototype and metabolites that were identified were subsequently quantified using positive electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 387.4→369.6 and 387.4→351.3 for bufalin, m/z 513.7→145.3 for IS, and 387.4→369.6, 419.2→365.2, and 403.2→349.2 for the main metabolites (3-epi-bufalin, dihydroxylated bufalin, and hydroxylated bufalin, respectively). The method was validated over the calibration curve range of 1.00–100 ng/mL with a limit of quantitation (LOQ) of 1 ng/mL for bufalin. No obvious matrix effect was observed, and the intra- and inter-day precisions, as well as accuracy, were all within the acceptable criteria in this method. Then, this method was successfully applied in metabolic profiling and a pharmacokinetic study of bufalin after an oral administration of 10 mg/kg to rats. The method of simultaneous determination of bufalin and its nine metabolites in rat plasma could be useful for pharmacokinetic–pharmacodynamic relationship research of bufalin, providing experimental evidence for explaining the occurrence of some adverse effects of Venenum Bufonis and its related preparations.

scholarly journals Simultaneous Determination of 13 Constituents of Radix Polygoni Multiflori in Rat Plasma and Its Application in a Pharmacokinetic Study

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Wenhao Cheng ◽  
Yinghui Li ◽  
Wei Yang ◽  
Siyang Wu ◽  
Mengmeng Wei ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Pharmacokinetic Study ◽  
Matrix Effects ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Limit Of Quantitation ◽  
Negative Ionization Mode ◽  
Negative Ionization

Radix Polygoni Multiflori (RPM) has been widely used to treat various diseases in Asian countries for many centuries. Although, stilbenes and anthraquinones, two major components of RPM, show various bioactive effects, it has been speculated that the idiosyncratic hepatotoxicity induced by RPM may be related to these constituents. However, information on the pharmacokinetics of stilbenes and anthraquinones at a subtoxic dose of RPM is limited. A simple and sensitive UPLC-MS/MS bioanalytical method for the simultaneous determination of 13 ingredients of RPM, including chrysophanol, emodin, aloe-emodin, rhein, physcion, questin, citreorosein, questinol, 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside, torachrysone-8-O-glucoside, chrysophanol-8-O-β-D-glucoside, emodin-8-O-β-D-glucoside, and physcion-8-O-β-D-glucoside, in rat plasma was established. Acetonitrile was employed to precipitate the plasma with appropriate sensitivity and acceptable matrix effects. Chromatographic separation was performed using a waters HSS C18 column with a gradient elution using water and acetonitrile both containing 0.025% formic acid within a run time of 9 min. The constituents were detected in negative ionization mode using multiple reaction monitoring. The method was fully validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects, and stability. The lower limit of quantitation of the analytes was 0.1–1 ng/mL. The intrabatch and interbatch accuracies were 87.1–109%, and the precision was within the acceptable limits. The method was applied to a pharmacokinetic study after oral administration of RPM extract to rats at a subtoxic dose of 36 g/kg.

scholarly journals Simultaneous Determination and Pharmacokinetic Comparisons of Multi-Ingredients after Oral Administration ofRadix Salviae MiltiorrhizaeExtract, Hawthorn Extract, and a Combination of Both Extracts to Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yu-Qiang Liu ◽  
Qian Cai ◽  
Chang Liu ◽  
Feng-Wei Bao ◽  
Zhen-Qiu Zhang
Keyword(s):  
Oral Administration ◽  
Simultaneous Determination ◽  
Pharmacokinetic Study ◽  
Rosmarinic Acid ◽  
Rat Plasma ◽  
Hplc Method ◽  
Radix Salviae Miltiorrhizae ◽  
Salviae Miltiorrhizae ◽  
Hawthorn Extract

A simple and sensitive HPLC method was developed for simultaneous determination of danshensu (DSS), rosmarinic acid (RA), lithospermic acid (LA), salvianolic acid B (SAB), and hyperoside (HP) in rat plasma. This method validated was successfully applied to the pharmacokinetic study of the main active ingredients after oral administration ofRadix Salviae Miltiorrhizaeextract (SME), hawthorn extract (HTE), and a combination of both extracts (2.5 : 1) to rats. The results indicated that there have been great differences in pharmacokinetics between a single extract and a combination of both extracts. A combination of both extracts can enhance their bioavailabilities and delay the elimination of SAB and DSS in rats.

Simultaneous Determination of Kirenol, Rosmarinic Acid and Caffeic Acid in Rat Plasma and Pharmacokinetic Study After Oral Administration of the Extract of Manxingshizhen Preparation by UPLC-MS/MS

2018 ◽  
Vol 15 (1) ◽  
pp. 74-81 ◽  
Author(s):  
Shuo Sun ◽  
Xue Zhang ◽  
Linda Luo ◽  
Ping Wang ◽  
Mengxuan Bai ◽  
...  
Keyword(s):  
Oral Administration ◽  
Electrospray Ionization ◽  
Simultaneous Determination ◽  
Caffeic Acid ◽  
Pharmacokinetic Study ◽  
Rosmarinic Acid ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Tandem Mass Spectrometric

Introduction: A rapid, sensitive and convenient ultra-performance liquid chromatography with tandem mass spectrometric detection (UPLC-MS/MS) method has been validated and applied to the simultaneous determination of kirenol, rosmarinic acid and caffeic acid after oral administration of the extract of Manxingshizhen preparation in rat plasma. Materials and Methods: Puerarin was selected as the internal standard (IS). The plasma sample preparation was pretreated by liquid-liquid extraction of the mixture with ethyl acetate. All analytes were simultaneously detected in multiple reaction monitoring (MRM) mode via both the positive electrospray ionization (ESI+) and negative electrospray ionization (ESI). In the experiment, all calibration curves revealed good linearity (r > 0.999). The LLOQ were between 0.80-2.00 ng/mL, respectively. Besides, the intra-day and inter-day precision ranged from 6.4 to 13.8%, respectively. Moreover, the accuracy was within - 11.4% and 12.8% for all the QC levels of all analytes. The extraction recoveries of the analytes and IS in plasma at three concentration levels ranged from 88.5 to 103.2%, moreover, the matrix effects of all the analytes and the IS were found to be satisfied with the acceptable range of 89.8%-101.7%. Meanwhile, the RSD values of stability met the requirement of not more than 15%. Furthermore, the pharmacokinetic parameters of three compounds were analyzed using concentrationtime profiles. Conclusion and Results: Plasma concentrations of the three compounds were determined up to 24 h after oral administration, and their pharmacokinetic parameters were in agreement with previous studies. The validated method was successfully applied in a pharmacokinetic study in rat plasma after oral administration of Manxingshizhen preparation.

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