scholarly journals Toxicokinetics of 11 Gelsemium Alkaloids in Rats by UPLC-MS/MS

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xiuwei Shen ◽  
Jianshe Ma ◽  
Xianqin Wang ◽  
Congcong Wen ◽  
Meiling Zhang
Keyword(s):  
Intravenous Administration ◽  
Matrix Effects ◽  
Scientific Evidence ◽  
Simultaneous Detection ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Sprague Dawley ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Main Components

Gelsemium elegans (Gardn. & Champ.) Benth. is a plant belonging to the genus Gelsemium (family Gelsemiaceae), and its main components are alkaloids. It is a Chinese traditional medicinal plant and notoriously known as a highly toxic medicine. However, a method has not yet been found for the simultaneous detection of 11 Gelsemium alkaloids in rat plasma, and the toxicokinetics of 11 Gelsemium alkaloids after intravenous administration has not been reported. In this work, we have developed a sensitive and rapid method of ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) for the detection of 11 Gelsemium alkaloids in rat plasma. The toxicokinetic behavior was also investigated, so as to provide a reference of the scientific properties of Gelsemium elegans and improve the efficacy and safety of drugs. Sixty-six Sprague-Dawley rats were randomly divided into 11 groups, six rats in each group. Each group was intravenously given one alkaloid (0.1 mg/kg), respectively. A Waters UPLC BEH C18 column (50 mm×2.1 mm, 1.7 μm) was used for chromatographic separation. Methanol and water (containing 0.1% formic acid) were used for the mobile phase with gradient elution. Multiple reactions were monitored, and positive electrospray ionization was used for quantitative analysis. The precision was less than 16%, and the accuracy was between 86.9% and 113.2%. The extraction efficiency was better than 75.8%, and the matrix effects ranged from 88.5% to 107.8%. The calibration curves were in the range of 0.1–200 ng/mL, with a correlation coefficient (R2) greater than 0.995. The UPLC-MS/MS method was successfully applied to the toxicokinetics of 11 Gelsemium alkaloids in rats after intravenous administration (0.1 mg/kg for each alkaloid). The results of the toxicokinetics provide a basis for the pharmacology and toxicology of Gelsemium alkaloids and scientific evidence for the clinical use of Gelsemium alkaloids.

scholarly journals Development and Validation of a Sensitive, Specific and Reproducible UPLC-MS/MS Method for the Quantification of OJT007, A Novel Anti-Leishmanial Agent: Application to a Pharmacokinetic Study

2021 ◽  
Vol 18 (9) ◽  
pp. 4624
Author(s):  
Maria Rincon Nigro ◽  
Jing Ma ◽  
Ololade Tosin Awosemo ◽  
Huan Xie ◽  
Omonike Arike Olaleye ◽  
...  
Keyword(s):  
Formic Acid ◽  
High Performance ◽  
Leishmania Major ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Positive Mode ◽  
Acquity Uplc

OJT007 is a methionine aminopeptidase 1 (MetAP1) inhibitor with potent anti-proliferative effects against Leishmania Major. In order to study its pharmacokinetics as a part of the drug development process, a sensitive, specific, and reproducible ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated. Voriconazole was used as the internal standard to generate standard curves ranging from 5 to 1000 ng/mL. The separation was achieved using a UPLC system equipped with an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) with 0.1% formic acid in acetonitrile and 0.1% formic acid in water as the mobile phase under gradient elution at a flow rate of 0.4 mL/min. The mass analysis was performed with a 4000 QTRAP® mass spectrometer using multiple-ion reaction monitoring (MRM) in the positive mode, with the transition of m/z 325 → m/z 205 for OJT007 and m/z 350 → m/z 101 for voriconazole. The intra- and inter-day precision and accuracy were within ±15%. The mean extraction recovery and the matrix effect were 95.1% and 7.96%, respectively, suggesting no significant matrix interfering with the quantification of the drug in rat plasma. This study was successfully used for the pharmacokinetic evaluation of OJT007 using the rat as an animal model.

scholarly journals Development and Validation of a UPLC-MS/MS Method for the Quantitative Determination and Pharmacokinetic Analysis of Cirsimarin in Rat Plasma

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
En Zhang ◽  
Ying Wang ◽  
Fuyi Xie ◽  
Xinlei Zhuang ◽  
Xianqin Wang ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
High Performance ◽  
Rat Plasma ◽  
Biological Properties ◽  
Pharmacokinetic Analysis ◽  
Standard Curve ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Development And Validation

Cirsimarin is a bioactive antilipogenic flavonoid isolated from the cotyledons of Abrus precatorius and represents one of the most abundant flavonoids present in this plant species. Cirsimarin exhibits excellent antioxidant, lipolysis, and other biological properties; it can effectively trigger lipid movement and demonstrates antiobesity effects. In this work, an ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of cirsimarin in rat plasma after intravenous administration. A standard curve of cirsimarin in blank rat plasma was generated over the concentration range of 1–3000 ng/mL. Six rats were administered cirsimarin intravenously (1 mg/kg). The method only required 50 μL of plasma for sample preparation, and the plasma proteins were precipitated with acetonitrile to pretreat the plasma sample. The precisions of cirsimarin in rat plasma were less than 14%, while the accuracies varied between 92.5% and 107.3%. In addition, the matrix effect varied between 103.6% and 107.4%, while the recoveries were greater than 84.2%. This UPLC-MS/MS method was then applied in measuring the pharmacokinetics of cirsimarin in rats. The AUC(0-t) values of cirsimarin from the pharmacokinetic analysis were 1068.2 ± 359.2  ng/mL·h for intravenous administration. The half-life ( t 1 / 2 ) was 1.1 ± 0.4  h (intravenous), indicating that the metabolism of the compound was quick in the rats. Exploring the pharmacokinetics of cirsimarin in vivo can help better understand its metabolism.

Pharmacokinetic Study of Deltaline in Mouse Blood Based on UPLCMS/ MS

2019 ◽  
Vol 15 (2) ◽  
pp. 194-199 ◽  
Author(s):  
Huanchun Song ◽  
Yiwei Huang ◽  
Dongqing Zhu ◽  
Shuhua Tong ◽  
Meiling Zhang ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Mouse Blood ◽  
Limit Of Quantitation ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Precipitate Protein

Introduction: Deltaline, an aconitine-type alkaloid, was detected in mouse blood using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method, and the pharmacokinetics of deltaline following intravenous administration in mice was studied. </P><P> Materials and Methods: The gelsenicine was used as the internal standard (IS). Deltaline and IS were eluted at a flow rate of 0.4 ml/min and separated on a UPLC BEH C18 column by gradient elution using acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid) as a mobile phase. The following transitions were obtained at m/z 508.2→75.0 for deltaline and m/z 327.1→107.8 for gelsenicine in multiple reactions monitoring mode. Acetonitrile was used to precipitate protein. Six mice after intravenous administration of a single dose of deltaline (1 mg/kg), 20-µL blood samples from each mouse were collected from the tail vein. Results: The UPLC-MS/MS method was sensitive and linear (r>0.995) with a lower limit of quantitation (LLOQ) of 0.1 ng/mL over the range of 0.1-500 ng/mL. Intra- and inter-day precisions were below 13%, the accuracy range was between 88.0% and 108.2%, the recovery was higher than 90.1%, and the matrix effect was between 102.9% and 108.1%. Conclusion: The method was sensitive, fast, specific, and has been successfully applied to a pharmacokinetic study of deltaline after intravenous administration.

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.

scholarly journals Simultaneous Determination of Five Components of Chaihu-Shugan-San in Beagle Plasma by HPLC-MS/MS and Its Application to a Pharmacokinetic Study after a Single Dose of Chaihu-Shugan-San

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yong-liang Zhu ◽  
Hui-jun Wang ◽  
Hao Xue ◽  
Yi Zhang ◽  
Qian-shi Cheng ◽  
...  
Keyword(s):  
Single Dose ◽  
High Performance ◽  
Matrix Effects ◽  
Gradient Elution ◽  
Gastrointestinal Diseases ◽  
Column Temperature ◽  
Mobile Phases ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Total Measurement Time

Chaihu-shugan-san (CHSGS) has been widely used in China to treat depression and gastrointestinal diseases for thousands of years, but little is known about its pharmacokinetic properties. The purpose of our study is to develop a reliable and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to detect five components in beagle plasma and study their pharmacokinetic after oral administration of CHSGS in beagles. An Agilent C18 column (2.1 × 150 mm, 3.5 μm) was used to separate the analytes, and the column temperature was maintained at 40°C. A gradient elution procedure was used with solvent A (acetonitrile) and solvent B (0.1% formic acid, aqueous) as mobile phases. The elution procedure was 60% B—10% B (0–3 min) and 10% B—60% B (3.1–4 min). The flow rate was 0.3 mL/min, and the total measurement time was 4 min. Within the determined range, the standard calibration curves of the five analytes had a satisfactory linear relationship (r2 ≥ 0.9923). The recovery rate (n = 6) of the five analytes was between 85.42% and 90.85%, and the matrix effects (n = 6) were between 94.52% and 103.91%. These results show that the validated method could be successfully applied to study the pharmacokinetic in beagles after a single dose of CHSGS.

Fully-Automated SPE Coupled to UPLC-MS/MS Method for Simultaneous Detection of Trace Sulfonamides, Quinolones, and Macrolide antibiotics in Water

2021 ◽  
Author(s):  
Ming Zheng ◽  
Suwen Tang ◽  
Yangyang Bao ◽  
Kevin D Daniels ◽  
Zuo Tong How ◽  
...  
Keyword(s):  
High Performance ◽  
Matrix Effects ◽  
Solid Phase ◽  
Yangtze River Basin ◽  
Pure Water ◽  
Simultaneous Detection ◽  
Sample Volume ◽  
Relative Standard ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass

Abstract A fully automated solid-phase extraction (SPE) coupled ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed for analysis of antibiotics (sulfonamides, quinolones, and macrolide) in water matrices. Sample preparation optimization included the selection of the best SPE material and configuration (HLB disks), sample volume (500−1000 mL water sample (pH = 3)) with a flow rate at 1−2 mL min− 1, and an elution procedure with 2 ⋅ 6 mL methanol, 2 ⋅ 6 mL acetone-methanol (V/V = 1/1). Meanwhile, the parameters for UPLC-MS/S detection of each analyte was optimized, including LC retention time, and MS parameters. The instrumental limits of detection (LOD) and quantification (LOQ) of analytes ranged from 0.01−0.72 µg L− 1 and 0.05−2.39 µg L− 1, respectively, with good linear correlation (R2 > 0.995) and precision (< 9.9%). Matrix spike recoveries ranged between 63.3−99.2% in pure water, 60.8−91.3% in surface water (SW), and 59.9−102.8% in wastewater effluent (WWE) with relative standard deviations (RSD) below 11%. The matrix effects (MEs) observed for most of the analytes were ion suppression (0−25.8%) except for four compounds that had enhancement (0−8.0 %) in SW or WWE. This method can basically meet the needs of trace antibiotic residues detection in waters. Trace levels of sulfonamides, quinolones and macrolides using the developed antibiotic method were below LOQ (BQL) −94.47 ng L− 1 in WWEs and BQL−15.47 ng L− 1 in SW in the lower reaches of the Yangtze River Basin.

scholarly journals Simultaneous Determination of 11 Compounds in Gualou Guizhi Granule and Pharmacokinetics Study by UPLC-MS/MS

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Chengtao Sun ◽  
Wen Xu ◽  
Yuqin Zhang ◽  
Lishuang Yu ◽  
Miao Ye ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Negative Ion ◽  
Detection Range ◽  
Pharmacokinetics Study ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Negative Ion Mode

A rapid and sensitive ultrafast performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) was developed for the simultaneous determination of 11 compounds in Gualou Guizhi Granule (GLGZG), including liquiritin, isoliquiritin, liquirtin apioside, isoliquiritin apioside, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, paeoniflorin, albiflorin, and paeoniflorin sulfonate in rat plasma. UPLC-MS/MS assay with negative ion mode was performed on a Waters CORTECS C18 (2.1 × 100 mm, 1.6 μm) with the mobile phase consisting of 0.1% aqueous formic acid (A) and acetonitrile (B) in gradient elution at a flow rate of 0.25 mL·min−1. The method was linear for all analytes within the detection range (r≥0.9597). The inter- and intraday precision (RSD) were 2.21–6.41% and 1.67–6.18%; the inter- and intraday accuracy (recover) were 92.48–114.03% and 90.23–112.04%. And the recovery rate ranged from 81.30% to 108.22%. The matrix effect values obtained for analytes ranged from 88.91% to 113.32%. This validated method was successfully applied to a pharmacokinetics study in rats after oral administration of GLGZG.

scholarly journals Pharmacokinetics of isocorynoxeine in rat plasma after intraperitoneal administration by UPLC–MS/MS

2020 ◽  
Vol 32 (4) ◽  
pp. 260-263
Author(s):  
Haichao Zhan ◽  
Zhen Wei ◽  
Ke Ren ◽  
Shuhua Tong ◽  
Xianqin Wang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Intraperitoneal Administration ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Relative Standard ◽  
Liquid Chromatography Tandem Mass

Isocorynoxeine is one of the main alkaloids in Chinese medicinal herbs, and has pharmacological activities such as antihypertensive, sedative, anticonvulsant, and neuronal protection. It is an effective component of Uncaria for the treatment of hypertension. In this study, we used a fast and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) to detect isocorynoxeine in rat plasma and investigated its pharmacokinetics in rats. Six rats were given isocorynoxeine (15 mg/kg) by intraperitoneal (i.p.) administration. Blood (100 μL) was withdrawn from the caudal vein at 5 and 30 min and 1, 2, 4, 6, 8, 12, and 24 h after administration. Chromatographic separation was achieved using a UPLC BEH C18 column using a mobile phase of acetonitrile–0.1% formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in the multiple reaction monitoring (MRM) mode with positive ionization was applied. Intra-day and inter-day precisions (relative standard deviation, %RSD) of isocorynoxeine in rat plasma were lower than 12%. The method was successfully applied in the pharmacokinetics of isocorynoxeine in rats after intraperitoneal administration. The t1/2 of isocorynoxeine is 4.9 ± 2.1 h, which indicates quick elimination.

scholarly journals An LC-MS/MS Method for Simultaneous Determination of the Toxic and Active Components of Cortex Periplocae in Rat Plasma and Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Li ◽  
Yang Li ◽  
Jin Li ◽  
Rui Liu ◽  
Jia Hao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Simple Liquid ◽  
Active Components ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass

A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the toxic and other active components including isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract to rats. Plasma samples were prepared by protein precipitation with methanol. All compounds were separated on a C18 column with gradient elution using acetonitrile and formic acid aqueous solution (0.1%, v/v) as the mobile phase at a flow rate of 0.3 mL/min. The detection of all compounds was accomplished by multiple-reaction monitoring (MRM) in the positive electrospray ionization mode. The LC-MS/MS method exhibited good linearity for five analytes. The lower limit of quantification (LLOQ) was 0.48 ng/mL for scopoletin, periplogenin, and periplocymarin; 2.4 ng/mL for isovanillin and periplocin. The extraction recoveries of all compounds were more than 90% and the RSDs were below 10%. It was found that the absorption of scopoletin and periplocin was rapid in vivo after oral administration of cortex periplocae extract. Furthermore, periplocymarin possessed abundant plasma exposure. The results demonstrated that the validated method was efficiently applied for the pharmacokinetic studies of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract.

scholarly journals A New UPLC-MS/MS Method Validated for Quantification of Jervine in Rat Plasma and the Study of Its Pharmacokinetics in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Lianguo Chen ◽  
Qinghua Weng ◽  
Jianshe Ma
Keyword(s):  
Lower Limit ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Limit Of Determination ◽  
Limit Of Quantitation ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Reactive Monitoring ◽  
Interday Precision

The aim of this study was to develop an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to assess the concentration of jervine in rat plasma and its pharmacokinetics. Diazepam was used as internal standard (IS). The chromatographic separation of jervine and IS was carried out on an UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with a flow rate of 0.4 mL/min. A mixture of acetonitrile and water (0.1% formic acid) was used as a mobile phase. The UPLC-MS/MS was equipped with an electrospray ionization (ESI), adopting multiple reactive monitoring mode to determine jervine in rat plasma. The retention times of jervine and the internal standard were 1.71 and 2.13 min, respectively. The calibration curve of jervine ranged between 1 and 1000 ng/mL. The lower limit of quantitation (LLOQ) was 1 ng/mL, and the lower limit of determination (LLOD) was 0.2 ng/mL. The accuracy was ±6%; the interday precision and intraday precision were no more than 9%. The recovery was higher than 90.3%, and the matrix effect was lower than 10%. The UPLC-MS/MS method was successfully developed and used for the application of the pharmacokinetic study. The primary pharmacokinetic parameters of jervine in this study were as follows: the AUC(0–∞) was 969.3 ± 277.7 ng/mL·h, the Cmax was 506.6 ± 192.8 ng/mL, the CL/F was 1.7 ± 0.5 L/h/kg, and the t1/2 was 3.4 ± 1.2 h.

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