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 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.

A Validated LC–MS/MS Method for the Simultaneous Determination of Ticagrelor, Its Two Metabolites and Major Constituents of Tea Polyphenols in Rat Plasma and Its Application in a Pharmacokinetic Study

2021 ◽  
Author(s):  
Ying Xue ◽  
Ziteng Wang ◽  
Weimin Cai ◽  
Xin Tian ◽  
Shuaibing Liu
Keyword(s):  
Simultaneous Determination ◽  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Plasma Concentrations ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Tea Polyphenols ◽  
Bioanalytical Method Validation

Abstract Ticagrelor is recommended for management of patients with acute coronary syndromes. Green tea is one of the most popular beverages in China and around the world. Their concomitant use is unavoidable. In this study, a selective and sensitive liquid chromatography–tandem mass spectrometry method for the simultaneous determination of plasma concentrations of ticagrelor, its two metabolites and four major constituents of tea polyphenols (TPs) in rats was developed for co-administration study of ticagrelor and TPs. Diazepam was used as internal standard (IS). Plasma samples were extracted employing a liquid–liquid extraction technique. Chromatographic separation was carried out on a Kinetex C18 column (2.1 × 75 mm, 2.6 μm) by gradient elution using 0.1% formic acid in water, acetonitrile and methanol. Seven analytes and IS were detected by a mass spectrometer with both positive and negative ionization by multiple reaction monitoring mode. The method was fully validated to be reliable and reproducible in accordance with food and drug administration (FDA) guidelines on bioanalytical method validation. The method was then successfully applied for pharmacokinetic study of ticagrelor, its two metabolites and four major constituents of TPs in rat plasma after oral administration of ticagrelor and tea polyphenol extracts.

scholarly journals Simultaneous Determination of Six Uncaria Alkaloids in Mouse Blood by UPLC–MS/MS and Its Application in Pharmacokinetics and Bioavailability

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Lianguo Chen ◽  
Jianshe Ma ◽  
Xianqin Wang ◽  
Meiling Zhang
Keyword(s):  
Simultaneous Determination ◽  
Oral Absorption ◽  
Matrix Effects ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Mouse Blood ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass

A specific ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the simultaneous determination of six Uncaria alkaloids in mouse blood with midazolam as the internal standard (IS). Only 20 μL blood was needed for sample preparation, and the protein was precipitated with acetonitrile. The UPLC BEH C18 column (2.1 mm×100 mm, 1.7 μm) was used for chromatographic separation. The mobile phase consisted of 0.1% formic acid and acetonitrile with gradient elution within 5.5 min. Multiple reaction monitoring (MRM) and the positive electrospray ionization model were used for quantitative analysis. The accuracy of the UPLC-MS/MS method ranged from 86.5% to 110.4%. The precision for intraday and interday was ≤15% each. The mean recovery and the matrix effects were found to be 64.4-86.8% and 94.1-109.4%, respectively. The calibration curves in blood were linear in the range of 1-1000 ng/mL with a favorable correlation coefficient (r2) of 0.995. The pharmacokinetic results showed that six Uncaria alkaloids metabolized rapidly in mice with a half-life between 0.6 h and 4.4 h. The bioavailability of corynoxeine, isocorynoxeine, rhynchophylline, isorhynchophylline, hirsutine, and hirsuteine was 27.3%, 32.7%, 49.4%, 29.5%, 68.9%, and 51.0%, respectively, which showed satisfactory oral absorption of each alkaloid.

Simultaneous Determination of Quercitrin, Afzelin, Amentoflavone, Hinokiflavone in Rat Plasma by UFLC–MS-MS and Its Application to the Pharmacokinetics of Platycladus orientalis Leaves Extract

2018 ◽  
Vol 56 (10) ◽  
pp. 895-902 ◽  
Author(s):  
Chen-xiao Shan ◽  
Shu-chen Guo ◽  
Sheng Yu ◽  
Ming-qiu Shan ◽  
Sam Fong Yau Li ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Platycladus Orientalis ◽  
Chromatography Tandem Mass Spectrometry ◽  
Relative Standard ◽  
Liquid Chromatography Tandem Mass

Abstract Leaves of Platycladus orientalis have been used as blood cooling and homeostatic therapy for thousands of years in traditional Chinese medicine. Emerging evidences of modern pharmacology have proved flavonoids as the key elements responsible for the efficacies. However, there has been no report on pharmacokinetic study of the flavonoids from Platycladus orientalis leaves extract. In this study, a sensitive and rapid ultra-flow liquid chromatography-tandem mass spectrometry method was established and validated for the simultaneous determination of amentoflavone, afzelin, hinokiflavone and quercitrin in rat plasma. The four flavonoids and luteolin (internal standard, IS) were recovered from rat plasma by methanol–ethyl acetate (v:v, 50:50). Chromatographic separation was performed on a C18 column with gradient elution. Our results showed that the recoveries from spiked control samples were more than 85% for all analytes and IS. The relative standard deviations of intra-day and inter-day precision were within 15% while the REs ranged from −6.6% to 8.0%. The validated method in this study was successfully applied to pharmacokinetic study in healthy rats after oral administration of P. orientalis leaves extract.

A UPLC-MS/MS Method for Simultaneous Determination of Six Bioactive Compounds in Rat Plasma, and its Application to Pharmacokinetic Studies of Naoshuantong Granule in Rats

2019 ◽  
Vol 15 (3) ◽  
pp. 231-242
Author(s):  
Ping Wang ◽  
Shenmeng Jiang ◽  
Yu Zhao ◽  
Shuo Sun ◽  
Xiaoli Wen ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Negative Ion ◽  
Pharmacokinetic Studies ◽  
Acquity Uplc

Background: It is urgently needed to clarify the pharmacokinetic mechanism for the multibioactive constituents in Traditional Chinese Medicines for its clinical applications. A rapid, sensitive and reliable ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of Danshensu, Ferulic acid, Astragaloside IV, Naringin, Neohesperidin and Puerarin after oral administration of Naoshuantong Granule using Carbamazepine as internal standard (IS). Methods: The plasma samples were pretreated by liquid-liquid extraction method using ethyl acetate after acidification, and separated on a Waters ACQUITY UPLC® BEH C18 column (50×2.1 mm, i.d., 1.7 µm) by gradient elution with a mobile phase composing of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.2 mL/min. Multiple reaction monitoring (MRM) mode with both positive and negative ion mode was operated using an electrospray ionization (ESI) to detect the six compounds. Result: All calibration curves showed good linearity (r>0.99) over a wide concentration range. The intra- and inter-day precision (RSD%) was below 8.4% and the accuracy (RE%) ranged from 91.1% to 107.5%. The extraction recoveries of the six analytes and IS in the plasma were more than 77.9% and no severe matrix effect was observed. Conclusion: The fully validated method was successfully applied to the pharmacokinetics of Naoshuantong Granule.

A Validated LC–MS/MS Method for Simultaneous Determination of 3-O-Acetyl-11-Keto-β-Boswellic Acid (AKBA) and its Active Metabolite Acetyl-11-Hydroxy-β-Boswellic Acid (Ac-11-OH-BA) in Rat Plasma: Application to a Pharmacokinetic Study

2020 ◽  
Vol 58 (6) ◽  
pp. 485-493
Author(s):  
Tarun Sharma ◽  
Snehasis Jana
Keyword(s):  
Simultaneous Determination ◽  
Pharmacokinetic Study ◽  
Active Metabolite ◽  
Dynamic Range ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Boswellic Acid ◽  
Mass Detection

Abstract The aim of this study was to develop and validate a new, rapid, sensitive, selective and reliable liquid chromatography–tandem mass spectrometry method for simultaneous determination of 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) and its active metabolite 3-O-Acetyl-11-hydroxy-β-boswellic acid (Ac-11-hydroxy-BA) in rat plasma. Both analytes (AKBA and Ac-11-hydroxy-BA) and the internal standard (IS, ursolic acid) were extracted from 100 μL of rat plasma by protein precipitation. Chromatographic separation was achieved on PRP-H1 RP-C18 column (75 mm × 2 mm, 1.6 μm) using acetonitrile–water (95.5 v/v) as the mobile phase. Mass detection was conducted by electrospray ionization in positive ion multiple reaction monitoring (MRM) mode. A linear dynamic range of 1–1,000 ng/mL for both AKBA and Ac-11-hydroxy-BA was established with mean correlation coefficient (r (1)) of 0.999. Intra- and inter-day precision (% CV) of analysis were found in the range of 1.9–7.4%. The accuracy determined for these analytes ranged from 92.4 to 107.2%. The extraction recoveries for both analytes ranged from 92.6 to 97.3% for spiked plasma samples and were consistent. The % change in stability samples compared to nominal concentration ranged from 0.4 to 4.2%. This method was successfully tested to a pharmacokinetic (PK) study for estimation of AKBA and acetyl-11-hydroxy-BA in rat plasma following oral administration of AKBA. This method has been validated with the advantage of shorter run time that can be used for high-throughput analysis and has been successfully applied to the pharmacokinetic study of AKBA in rats.

Simultaneous Determination of Eight Potential Q-Markers in Zishen Tongguan Capsules Based on UHPLC-MS/MS

2020 ◽  
Vol 17 (1) ◽  
pp. 47-56
Author(s):  
Shun Liu ◽  
Xun Wang ◽  
Kaiping Zou ◽  
Wei Liu ◽  
Cunyu Li ◽  
...  
Keyword(s):  
Quality Control ◽  
Chinese Medicine ◽  
Simultaneous Determination ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Quality Markers ◽  
High Repeatability ◽  
Comprehensive Study

Background: Zishen Tongguan (ZSTG) capsules were prepared at the Affiliated Hospital of Nanjing University of Chinese Medicine and have been proven to be clinically effective for treating pyelonephritis and benign prostatic hyperplasia. However, the quality standards are not ideal; a comprehensive study of the “quality markers” (Q-markers), the chemicals inherent in traditional Chinese medicine and its preparations, has not been carried out. Experimental Methods: In this paper, a sensitive and specific ultra-high-performance liquid chromatographictandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of eight potential Q-markers of ZSTG, including timosaponin A3, berberine, jatrorrhizine, phellodendrine, palmatine, mangiferin, neomangiferin, and timosaponin BII. A Kromasil 100-3.5 C18 column was used with a mobile phase of 0.2% formic acid with acetonitrile, and gradient elution at a flow rate of 0.2 mL/min was achieved in 13 minutes and used for separation. Detection was performed in positive/negative mode with multiple reaction monitoring (MRM). Results: The analytical method was validated in terms of the sensitivity, linearity, accuracy, precision, repeatability, stability and recovery. The method established here was successfully applied to study the potential Q-markers in 8 batches of commercial samples, which demonstrated its use in improving the quality control of ZSTG. Conclusion: The developed method had high repeatability and accuracy and was suitable for the simultaneous analysis of multiple Q-markers, which may provide a new basis for the comprehensive assessment and overall quality control of ZSTG.

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