scholarly journals A Validated LC-MS/MS Method for Simultaneous Determination of Six Aconitum Alkaloids and Seven Ginsenosides in Rat Plasma and Application to Pharmacokinetics of Shen-Fu Prescription

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Huizi Ouyang ◽  
Fang Liu ◽  
Zhidan Tang ◽  
Xiaopeng Chen ◽  
Fang Bo ◽  
...  
Keyword(s):  
Oral Administration ◽  
Simultaneous Determination ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Reaction Monitoring ◽  
Mass System ◽  
Acid Aqueous Solution ◽  
Interday Precision

A sensitive and reliable LC-MS/MS method has been developed and validated for simultaneous determination of six Aconitum alkaloids (aconitine, hypaconitine, mesaconitine, benzoylaconitine, benzoylhypacoitine, and benzoylmesaconine) and seven ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1) in rat plasma after oral administration of Shen-Fu prescription. Psoralen was selected as internal standard (IS). Protein precipitation with methanol was used in sample preparation. The chromatographic separation was achieved on a CORTECS™ C18 column with 0.1% formic acid aqueous solution and acetonitrile as mobile phase. The flow rate was 0.3 mL/min. The detection was performed on a tandem mass system with an electrospray ionization (ESI) source in the positive ionization and multiple-reaction monitoring (MRM) mode. The calibration curves of six Aconitum alkaloids and seven ginsenosides were linear over the range of 0.1-50 and 1-500 ng/mL, respectively. The extraction recoveries of the analytes in plasma samples ranged from 64.2 to 94.1%. Meanwhile, the intra- and interday precision of the analytes were less than 14.3%, and the accuracy was in the range of −14.2% to 9.8%. The developed method was successfully applied to the pharmacokinetics of six Aconitum alkaloids and seven ginsenosides in rat plasma after oral administration of Shen-Fu prescription.

scholarly journals Study on Pharmacokinetic and Bioavailability of Tamarixetin after Intravenous and Oral Administration to Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Jiayuan Shen ◽  
Qi Jia ◽  
Xuhua Huang ◽  
Guangzhe Yao ◽  
Wenjuan Ma ◽  
...  
Keyword(s):  
Oral Administration ◽  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Reaction Monitoring ◽  
Mass System ◽  
Intravenous And Oral Administration ◽  
Interday Precision

In this study, a sensitive and reliable HPLC-MS/MS method was established to quantify tamarixetin in rat plasma. This method was then applied to research on the pharmacokinetic and bioavailability of tamarixetin after intravenous and oral administration in vivo. The study was performed on CORTECS C18 column (4.6 mm × 150 mm, 2.7 μm) using mobile phase composed of methanol-water-formic acid (85 : 15 : 0.1, v/v) at a flow rate of 0.3 mL/min by a tandem mass system with an electrospray ionization (ESI) source in the negative multiple-reaction monitoring (MRM) mode. The calibration curves showed good linearity in the range of 5–4000 ng/mL. The intra- and interday precision of tamarixetin was less than 8.7% and 4.8%, respectively, and accuracy was within ±9.5%. Extraction recovery (91.4–100.0%) and matrix effect (99.4–107.4%) met the guidelines published by regulatory authorities. The oral bioavailability of tamarixetin was 20.3 ± 12.4%.

scholarly journals Simultaneous Determination of Ropivacaine and 3-Hydroxy Ropivacaine in Cerebrospinal Fluid by UPLC-MS/MS

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Siyuan Chen ◽  
Jianshe Ma ◽  
Xianqin Wang ◽  
Quan Zhou
Keyword(s):  
Cerebrospinal Fluid ◽  
Extraction Efficiency ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Reaction Monitoring ◽  
Limit Of Quantification ◽  
Liquid Liquid Extraction ◽  
The Matrix ◽  
Interday Precision

In this paper, a UPLC-MS/MS method was developed for the determination of ropivacaine and its metabolite 3-hydroxy ropivacaine in cerebrospinal fluid. The cerebrospinal fluid was processed by ethyl acetate liquid-liquid extraction. The multiple reaction monitoring (MRM) mode was used for quantitative analysis by monitoring the transitions of m/z 275.3 → 126.2 for ropivacaine, m/z 291.0 → 126.0 for 3-hydroxy ropivacaine, and m/z 290.2 → 198.2 for the internal standard. Standard curves for ropivacaine and 3-hydroxy ropivacaine in cerebrospinal fluid were conducted over the concentration range of 0.2–2000 ng/mL, demonstrating excellent linearity, and the lower limit of quantification was 0.2 ng/mL. The intraday precision of ropivacaine and 3-hydroxy ropivacaine was less than 11%, while the interday precision was less than 7%. The accuracy ranged between 87% and 107%, the average extraction efficiency was higher than 79%, and the matrix effect was between 89% and 98%. The developed method was then applied to a case of suspected poisoning of ropivacaine.

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.

Simultaneous determination of entecavir and lamivudine in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study

RSC Advances ◽  
2016 ◽  
Vol 6 (75) ◽  
pp. 70990-70998 ◽  
Author(s):  
Qikun Jiang ◽  
Yan Liu ◽  
Yunjie Wang ◽  
Yinghua Sun ◽  
Bo Li ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Multiple Reaction Monitoring ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Reaction Monitoring ◽  
Chromatography Tandem Mass Spectrometry ◽  
Mode Method ◽  
Liquid Chromatography Tandem Mass

The study's aim is to develop and validate a rapid, selective and sensitive ultra-performance liquid chromatography-tandem mass spectrometry with multiple reaction monitoring (MRM) mode method for the simultaneous determination of entecavir and lamivudine in rat plasma.

scholarly journals Determination of Anlotinib, a Tyrosine Kinase Inhibitor, in Rat Plasma by UHPLC-MS/MS and Its Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Zhe Wang ◽  
Le-jing Lian ◽  
Yan-yan Dong ◽  
Xiao Cui ◽  
Jian-chang Qian ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Kinase Inhibitor ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Reaction Monitoring ◽  
Receptor Kinase ◽  
Quadrupole Mass ◽  
Triple Quadrupole Mass Spectrometer

Anlotinib is a novel inhibitor of receptor kinase tyrosine with multitargets and has a broad spectrum of inhibitory action on tumor angiogenesis and growth. A simple and rapid UHPLC-MS/MS bioanalytical method was validated for the determination of anlotinib in rat plasma, using imatinib as an internal standard. An Acquity BEH C18 column was used to separate analytes. The eluents consisted of formic acid/water (0.1 : 100, v/v) and acetonitrile with a mobile phase. A triple quadrupole mass spectrometer was operated for the quantification with multiple reaction monitoring (MRM) to determine transitions: 408.2 ⟶ 339.1 for anlotinib, and 494.3 ⟶ 394.1 for imatinib. The validated range was 0.1–50 ng/mL for anlotinib. Mean recovery rate of anlotinib in plasma was ≥99.32% and reproducible. Also, the intra- and interday precisions were both below 15%. This robust method was successfully applied to support the pharmacokinetic study of anlotinib in rats.

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.

scholarly journals Determination and pharmacokinetics of calycanthine in rat plasma by UPLC-MS/MS

2020 ◽  
Author(s):  
Meifei Lu ◽  
Xiaojie Lu ◽  
Zheng Yu ◽  
Congcong Wen
Keyword(s):  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Precipitation Method ◽  
Absolute Bioavailability ◽  
Limit Of Quantification ◽  
The Matrix ◽  
Acid Aqueous Solution

AbstractCalycanthine is an important class of alkaloids extracted and isolated from the roots, leaves, flowers and fruits of Chimonanthus praecox. In this work, the UPLC-MS/MS method was used for determination of calycanthine in rat plasma, and the pharmacokinetics in rats were investigated. Midazolam was used as an internal standard (IS), and methanol precipitation method was used to pretreatment the rat plasma samples. Chromatographic separation was achieved on a UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column with the mobile phase of methanol- 0.1% formic acid aqueous solution with gradient elution. Multiple reaction monitoring (MRM) mode with positive ionization was applied for quantitative analysis, m/z 347.3 → 246.7 and 326.2 → 291.4 for calycanthine and IS, respectively. The results indicated that within the range of 1–200 ng/mL, linearity of calycanthine in rat plasma was good (r > 0.995), and the lower limit of quantification (LLOQ) was 1 ng/mL. Accuracy range was between 90.6 and 109.4%, precision (RSD) of calycanthine was less than 14%. The matrix effect was between 97.9% and 105.4%, the recovery was better than 85.6%. The developed UPLC-MS/MS method was successfully applied in the pharmacokinetics of calycanthine in rats after oral and intravenous administration. The absolute bioavailability of the calycanthine was 37.5% in rats.

scholarly journals A Validated HPLC-MS/MS Method for Simultaneous Determination of Militarine and Its Three Metabolites in Rat Plasma: Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Hui-Yuan Sun ◽  
Lin Zheng ◽  
Zi-Peng Gong ◽  
Yue-Ting Li ◽  
Chang Yang ◽  
...  
Keyword(s):  
Formic Acid ◽  
Simultaneous Determination ◽  
Multiple Reaction Monitoring ◽  
Area Under The Curve ◽  
Internal Standard ◽  
Rat Plasma ◽  
Relative Standard ◽  
Method Accuracy

A rapid, reliable, and sensitive HPLC-electrospray ionization-tandem mass spectrometry (HPLC-MS/MS) method was established and validated for simultaneous determination of militarine and its three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) in rat plasma. Plasma was acidified with formic acid, and protein was precipitated with methanol. MS/MS with ESI and multiple reaction monitoring at m/z 725.3→457.3, 457.1→127, 304.3→107.2, 189→129, and 417.1→267.1 was used for determination of militarine, gastrodin, α-isobutylmalic acid, gymnoside I, and puerarin (internal standard), respectively. Chromatographic separation was conducted using an ACE UltraCore SuperC18 (2.1 × 100 mm, 2.5 μm) column with gradient mobile phase (0.1% formic acid in water and acetonitrile). The lower limits of quantitation for militarine, gastrodin, α-isobutylmalic acid, and gymnoside I were 1.02, 2.96, 1.64, and 0.3 ng/mL, respectively. The relative standard deviations of intra- and interday measurements were less than 15%, and the method accuracy ranged from 87.4% to 112.5%. The extraction recovery was 83.52%-105.34%, and no matrix effect was observed. The three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) were synchronously detected at 0.83 h, suggesting that militarine was rapidly transformed to gastrodin, α-isobutylmalic acid, and gymnoside I. Moreover, the area under the curve (AUC) and Cmax of militarine were significantly lower than those of gastrodin and α-isobutylmalic acid, showing that militarine was largely metabolized to gastrodin and α-isobutylmalic acid in vivo. The studies on pharmacokinetics of militarine and its three metabolites were of great use for facilitating the clinical application of militarine and were also highly meaningful for the potential development of militarine.

Determination of Shanzhiside Methylester in Rat Plasma by Uplc-Ms/Ms and its Application to a Pharmacokinetic Study

2020 ◽  
Vol 16 (7) ◽  
pp. 960-966
Author(s):  
Qinghua Weng ◽  
Yichuan Chen ◽  
Zuoquan Zhong ◽  
Qianqian Wang ◽  
Lianguo Chen ◽  
...  
Keyword(s):  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Precipitation Method ◽  
Reaction Monitoring ◽  
Limit Of Quantification ◽  
Pharmacokinetics In Rats

Introduction: In this study, we used UPLC-MS/MS to detect shanzhiside methylester in rat plasma, and investigated its pharmacokinetics in rats. Materials and Methods: Diazepam was utilized as an internal standard (IS), and acetonitrile precipitation method was used to process the plasma samples. Chromatographic separation was achieved using a UPLC BEH C18 column using mobile phase of methanol-0.1 % formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in multiple reaction monitoring (MRM) mode with positive ionization was applied. Results: The results indicated that within the range of 5-4000 ng/mL, linearity of shanzhiside methylester in rat plasma was acceptable (r>0.995), and the lower limit of quantification (LLOQ) was 5 ng/mL. Intra-day and inter-day precision RSD of shanzhiside methylester in rat plasma were lower than 14%. Accuracy range was between 87.3 % and 109.1 %, and matrix effect was between 99.2% and 106.3%. Conclusion: The method was successfully applied in the pharmacokinetics of shanzhiside methylester in rats after intravenous administration.

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