Simultaneous Determination of Three Alkaloids in Wutou Decoction in Rat Plasma Via the UPLC–MS/MS Method and its Application in Pharmacokinetic Study

2020 ◽  
Vol 16 (5) ◽  
pp. 558-563
Author(s):  
WU Jian ◽  
JI Yu-bin ◽  
Liu Ying-jie ◽  
XU Ying ◽  
Zheng Wei ◽  
...  
Keyword(s):  
Electrospray Ionization ◽  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Intragastric Administration ◽  
Highly Sensitive ◽  
Pharmacokinetic Properties

Introduction: Wutou decoction has been wildly applied for the treatment of RA in China for several thousand years. Methods: This study aims to develop a highly sensitive and specific ultra performance liquid chromatography coupled with tandem mass spectrometry and electrospray ionization (UPLC-ESI-MS/MS) method to explore the pharmacokinetic properties of three representative bioactive alkaloids after intragastric administration of Wutou decoction in rats. Chromatographic separation was performed on a C18 column under the Multiple Reaction Monitoring (MRM) in the positive electrospray ionization (ESI) mode. The pharmacokinetic parameters were evaluated by software DAS 3. 0. Results: The validation of the method was achieved in accordance with the FDA guidelines. The results of pharmacokinetic study showed that the in vivo concentrations of benzoylmesaconine and benzoylhypaconine were significantly higher than benzoylaconine. Our PK results showed that these three compounds were quickly absorbed after the administration of Wutou decoction, and Tmax ranged from 30 min to 45 min. Conclusion: The results of pharmacokinetic study showed that the in vivo concentrations of benzoylmesaconine and benzoylhypaconine were significantly higher than benzoylaconine. There were also similar pharmacokinetic behaviors observed among BAC, BHA, and BMA after oral administration of WTD.

Simultaneous Determination of Four Bioactive Flavonoids in Rat Plasma by UPLC–MS/MS and Comparative Pharmacokinetic Study after Oral Administration of Danyikangtai Powder and Three Compatibilities

2020 ◽  
Vol 16 ◽  
Author(s):  
Yihe Huang ◽  
Yanhui Zhao ◽  
Yumeng Zhang ◽  
Lin Sun ◽  
Chunjie Zhao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Drug Candidate ◽  
Pharmacokinetic Parameters ◽  
Simultaneous Treatment ◽  
Scutellariae Radix

Background: Danyikangtai powder, a traditional Chinese medicine (TCM) formula, shows promise to become a novel drug candidate for the simultaneous treatment of chronic cholecystitis and chronic pancreatitis. However, the pharmacokinetic behavior of Danyikangtai powder remains unclear. Objective: We investigated the comparative pharmacokinetics of four flavonoids in rats after oral administration of Danyikangtai powder and three compatibilites. Materials and methods: The comparative pharmacokinetics was studied by ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS). Chromatographic separation was performed on an Universil XB-C18 column with a gradient mobile phase containing 0.1% (v/v) aqueous formic acid and acetonitrile. All analytes and internal standard were quantitated in the multiple reaction monitoring mode with a positive electrospray ionization interface. Results and discussion: Danyikangtai powder and Scutellariae radix have similar pharmacokinetic behaviors in rats after oral administration. However, the elimination of four flavonoids in rats after oral administration of Danyikangtai powder was accelerated, which was possibly related to the reduction of the potential hepatotoxicity of Scutellariae radix. The varying degrees of change in pharmacokinetic parameters after oral administration of different herb combinations suggested that herb–herb interactions occurred in vivo. Conclusions: This study will be helpful to reveal the safety, rational and mechanism of Danyikangtai powder formula compatibility, thereby providing pre-clinical research data for its new drug development and guidance for its rational clinical application.

scholarly journals Development of an UPLC–MS/MS assay to determine psoralidin in rat plasma and its application in a pharmacokinetic study after intragastric administration

2020 ◽  
Vol 32 (4) ◽  
pp. 215-218
Author(s):  
Feng Feng ◽  
Xiunan Jiang ◽  
Jieying Qiu ◽  
Hongyu Wu ◽  
Xiaojun Cai ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Apparent Volume ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Intragastric Administration ◽  
Rat Tissues ◽  
Pharmacokinetic Characteristic

Psoralidin has a variety of pharmacological activities, such as anti-tumor, anti-depressant, and anti-inflammatory activities. This study aims at developing a rapid ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method to determine psoralidin in rat plasma and studying the pharmacokinetic characteristic of psoralidin after intragastric administration of 20 and 40 mg/kg. Alpinetin was used as an internal standard (IS), and the plasma samples were precipitated with acetonitrile. The calibration curves were linear over the range of 0.2–250 ng/mL (R2 = 0.993). The pharmacokinetic parameters were calculated by DAS 3.0. Half-life (t1/2) was 7.2 ± 0.97 h and 7.1 ± 0.27 h for different dosages, respectively. Tmax was 4.2 ± 1.1 h and 4.0 ± 1.1 h for different dosages, respectively. Apparent volume of distribution (Vd) for different dosages was 630.1 ± 168.8 and 600.1 ± 138.8 L/kg, respectively. Clearance (CL) was 105.6 ± 29.2 and 100.6 ± 22.2 L/h/kg for different dosages, indicating that psoralidin was mainly distributed in rat tissues. The pharmacokinetic study provided important information for further clinical application in the treatment of cancer and osteoporosis.

scholarly journals Development and Validation of an Ultra-Performance Liquid Chromatography Method for the Determination of Wedelolactone in Rat Plasma and its Application in a Pharmacokinetic Study

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 762
Author(s):  
Qing Chen ◽  
Xiaoxue Wu ◽  
Xuemin Gao ◽  
Hua Song ◽  
Xuan Zhu
Keyword(s):  
Liquid Chromatography ◽  
Pharmacokinetic Study ◽  
Theoretical Basis ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Chromatography Method ◽  
Relative Standard

Wedelolactone is a coumarin ether with significant hepatoprotective effects. However, there are few pharmacokinetic studies of wedelolactone, which will affect the studies of its efficacy and potential toxicity. In this study, a selective ultra-performance liquid chromatography (UPLC) method was developed to confirm the pharmacokinetic parameters of wedelolactone in rat plasma. The chromatographic separation was carried out on a Kromasil C18 UPLC column (250 × 4.6 mm; 5.0 μm) by gradient mobile phase of methanol-water containing 0.5% acetic acid (v/v). Perfect linearity was obtained and the samples were stable under different conditions. The intra-day and inter-day precisions (relative standard deviation, %) were within 3.81% and accuracies (relative error, %) ranged from −4.01% to 7.12%. The extraction recoveries in rat plasma ranged from 95.98% to 108.93%. This rapid method was successfully applied in the pharmacokinetic study of wedelolactone in rat plasma. Following the oral administration of 5.00 mg/kg wedelolactone, the wedelolactone was rapidly absorbed. Pharmacokinetic parameters were used to quantitatively describe the dynamic changes of wedelolactone in vivo, providing a theoretical basis for pharmacological research on drugs and preclinical medication. The study of wedelolactone can provide a theoretical basis and quick analysis for the study of other traditional Chinese medicine. This may lead to breakthroughs in the pharmacokinetic study of complex Chinese medicines.

scholarly journals Simultaneous Quantification of Five Flavanone Glycosides in Rat Plasma by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry: Application to a Comparative Pharmacokinetic Study of Aurantii Fructus Immaturus and Aurantii Fructus Extracts

2019 ◽  
Vol 102 (3) ◽  
pp. 781-787 ◽  
Author(s):  
Pei Li ◽  
Su-Ling Zeng ◽  
Zi-Yuan Wang ◽  
Qiang Yin ◽  
Zhi-Ming Bi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Pharmacokinetic Study ◽  
Plasma Concentrations ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Tandem Mass ◽  
Liquid Chromatography Tandem Mass ◽  
Health Promoting

Abstract Background: Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) are two traditional citrus herbs with health-promoting and nutritive properties. Objective: This paper presents the first attempt to simultaneously investigate the absorption of five major flavanone glycosides, namely narirutin, naringin, hesperidin, neohesperidin, and poncirin, in rat plasma following a single oral administration of AFI and AF extracts to rats. Methods: The plasma concentrations were determined by liquid–liquid extraction followed by a rapid and sensitive ultra-performance LC-tandem mass spectrometry method. Pharmacokinetic parameters were analyzed by noncompartmental modeling using DAS software. Results: The developed method was validated and successfully applied to the pharmacokinetic study of these five flavanone glycosides. Conclusions: The comparison of the pharmacokinetic parameters of flavanone glycosides showed that the absorption of AF extract was lower, while the elimination was relatively rapid, compared with those of AFI extract. Highlights: This study may be useful for further utilization of these two citrus herbs.

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.

scholarly journals Simultaneous determination of two galangin metabolites from Alpinia Officinarum Hance in rat plasma by UF LC-MS/MS and its application in pharmacokinetics study

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11041
Author(s):  
Rangru Liu ◽  
Hailong Li ◽  
Na Wei ◽  
Yinfeng Tan
Keyword(s):  
Analytical Method ◽  
Glucuronic Acid ◽  
Multiple Reaction Monitoring ◽  
Ion Pairs ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Alpinia Officinarum ◽  
Negative Electrospray Ionization

Galangin has multiple pharmacological efficacies, such as anti-cancer, anti-inflammation and anti-oxidation. Galangin can be rapidly converted into glucuronidated metabolites in vivo. This study aimed to establish an UFLC-MS/MS analytical method to simultaneously determine the concentrations of two glucuronidated metabolites of galangin, galangin-3-O-β-D-glucuronic acid (GG-1) and galangin-7-O-β-D-glucuronic acid (GG-2) in rat plasma. After oral administration of galangal extract (0.3 g/kg), blood samples were collected from the orbital sinus, then treated by methanol precipitation and further gradient-eluted with Phenomenex Kinetex 2.6 µm XB-C18 column. The mass spectrometer was manipulated in the negative electrospray ionization (ESI) and selected multiple reaction monitoring (MRM) mode for the analytes. The precursor-to-product ion pairs applied for GG-1, GG-2 and chrysin (as the internal standard, IS) were m/z 445.2→269.0, 445.2→268.9 and 253.0→142.9, respectively. The results showed that the linear ranges for both GG-1 and GG-2 were 2.0–2000.0 ng/mL (r2 > 0.995). The inter- and intra-day precision were 89.3%–109.2%, RSD was less than 15%, and the repeatability was good. The recoveries of both metabolites and IS were over 89%, and matrix effect was within 15%. The validated analytical method was further applied to study the pharmacokinetic profiles of GG-1 and GG-2 in vivo. The pharmacokinetic parameters suggested that Tmax of GG-1 was equivalent to that of GG-2, and MRT0-t, t1/2 of GG-2 were a little higher than those of GG-1. Importantly, AUC0-t and Cmax of GG-2 were almost twice as those of GG-1. In short, the validated UFLCMS/MS analytical method was feasible to simultaneously determine two galangin metabolites GG-1 and GG-2 in rat plasma and further analyze in vivo metabolism of galangin.

A rapid and selective UPLC-MS/MS assay for accurate analysis of apatinib in rat plasma and its application to a pharmacokinetic study

2020 ◽  
Vol 16 ◽  
Author(s):  
Jinglin Gao ◽  
Zhangying Feng ◽  
Huan Ren ◽  
Mengdi Yu ◽  
Haidong Wang ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Kinase Inhibitor ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Flow ◽  
Treatment Method ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Accurate Analysis ◽  
Limit Of Quantitation

Objective: Apatinib, a novel small-molecule tyrosine kinase inhibitor (TKI), is under development to treat advanced gastric cancer. As to pharmacokinetic evaluation and routine drug monitoring of apatinib, a quantitative ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method in rat plasma was developed with tinidazole used as an internal standard (IS). Method: Protein precipitation (PPT) was selected as a sample pre-treatment method to extract apatinib. Then chromatography was performed on a Kinetex C8 column (2.1×100 mm, 2.6 μm) using a constant mobile phase including 0.2% formic acid and 10 mM ammonium acetate in water and methanol (30:70, v/v) with a gradient flow rate from 0.2 mL/min to 0.4 mL/min. Only 4.5 min was for a total chromatographic analysis. Mass spectrometric detection was carried on positive electrospray ionization (ESI+) mode with multiple-reaction monitoring (MRM). Results: Standard calibration curve showed good linearity in 2-1000 ng/mL with the correlation coefficient (R2) > 0.99. The lower limit of quantitation (LLOQ) was 2 ng/mL. The precision, accuracy, extraction recovery, matrix effect, stability and carryover were all within acceptable range. Conclusion: This method was simple, accurate, selective and successfully used for a pharmacokinetic study following seven rats orally administrated a single of 60 mg/kg apatinib.

Determination of JW5473 in Rat Plasma by UPLC-MS/MS and its Application to Pharmacokinetic Study of JW5473

Drug Research ◽  
2019 ◽  
Vol 69 (11) ◽  
pp. 606-611
Author(s):  
Tae Kon Kim
Keyword(s):  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Reversed Phase ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Esi Ms ◽  
Quantitation Limit ◽  
Fraction Absorbed

AbstractA sensitive method for quantitation of JW5473 in rat plasma has been established using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI/MS/MS). Tramadol was used as an internal standard. JW5473 and internal standard in plasma sample was extracted using acetonitrile (protein precipitation). A centrifuged upper layer was then evaporated and reconstituted with the mobile phase of 0.5% formic acid-acetonitrile (40:60, v/v). The reconstituted samples were injected into a C18 reversed-phase column. Using MS/MS in the multiple reaction monitoring (MRM) mode, JW5473 and tramadol were detected without severe interference from rat plasma matrix. JW5473 produced a protonated precursor ion ([M+H]+) at m/z 432.3 and a corresponding product ion at m/z 114.4. And the internal standard produced a protonated precursor ion ([M+H]+) at m/z 264.4 and a corresponding product ion at m/z 58.1. Detection of JW5473 in human plasma by the UPLC-ESI/MS/MS method was accurate and precise with a quantitation limit of 1.0 ng/mL. The validation, reproducibility, stability, and recovery of the method were evaluated. The method has been successfully applied to pharmacokinetic studies of JW5473 in rat plasma. Pharmacokinetic parameters of JW5473 was evaluated after intravenous (i. v.; at doses of 15 mg/kg) and oral (p.o.; at doses of 30 mg/kg) administration of JW5473 in rats. After p.o. administration (30 mg/kg) of JW5473, F (Fraction absorbed) value was approximately 70.5%.

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.

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