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

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.

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

Current Pharmaceutical Analysis ◽

10.2174/1573412915666181127151626 ◽

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.

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The UPLC-MS/MS Method for Determination of a Novel Enterovirus 71 Inhibitor in Rat Plasma and its Application to Pharmacokinetic Study

Current Pharmaceutical Analysis ◽

10.2174/1573412914666180924121855 ◽

2020 ◽

Vol 16 (2) ◽

pp. 117-124

Author(s):

Hai-Qiu Ma ◽

Chen-Qiang Zuo ◽

Ye Yuan ◽

Yu-Pu Zhang ◽

Xue Wang ◽

...

Keyword(s):

Pharmacokinetic Study ◽

Enterovirus 71 ◽

Internal Standard ◽

Ultra Performance Liquid Chromatography ◽

Rat Plasma ◽

Human Enterovirus ◽

Circulation System ◽

Pharmacokinetic Parameters ◽

Active Inhibitor ◽

Human Enterovirus 71

Background: TJAB1099 is a novel, highly active inhibitor of human enterovirus 71 (HEV71), which is a most commonly found virus leading to Hand-Foot-Mouth Disease (HFMD). However, the TJAB1099 could not be detected in the plasma using a regular HPLC-UV detection during the pharmacokinetic study due to the poor solubility, which in turn limited the release prior to be absorbed by the gastrointestinal tract. Objective: The objectives of the present study were to improve the solubility of TJAB1099 by preparing formulation and develop an Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) method applied to the pharmacokinetic study. Methods: The TJAB1099 was prepared as a phospholipid complex that intends to increase the watersolubility and subsequently improving TJAB1099 exposed in the circulation system. A highly sensitive UPLC-MS/MS method was developed for the pharmacokinetic study, in which the pharmacokinetic parameters were determined following oral and intravenous administration of 5 mg/kg and 1 mg/kg of TJAB1099 in rats, respectively. Results: The precisions for the method were less than 12.8%, while the accuracies were in the range of 90.8 - 98.0% and 96.1 - 99.6% for within-day and between-day, respectively. The mean recoveries for TJAB1099 and terfenadine (internal-standard, IS) were 85.0 ± 5.4% and 92.4 ± 4.1%, respectively. The pharmacokinetic study revealed that the Cmax of TJAB1099 after oral administration can reach 6.84 ± 2.43 ng/mL, while the Tmax is 0.70 ± 0.11 h. The AUC0-12 is 19.81 ± 11.07 µg/mL/h. However, the absorption was poor with an absolute oral bioavailability of 0.62. Conclusion: The UPLC-MS/MS method was successfully applied in the pharmacokinetic study of TJAB1099 in rats.

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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

Journal of AOAC International ◽

10.5740/jaoacint.18-0285 ◽

2019 ◽

Vol 102 (3) ◽

pp. 781-787 ◽

Cited By ~ 2

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.

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The Pharmacokinetics of Buserelin after Intramuscular Administration in Pigs and Cows

10.21203/rs.3.rs-900328/v1 ◽

2021 ◽

Author(s):

Zhengrong Gao ◽

Yu Liu ◽

Yuxin Yang ◽

Yuying Cao ◽

Jicheng Qiu ◽

...

Keyword(s):

Area Under The Curve ◽

Apparent Volume ◽

Ultra Performance Liquid Chromatography ◽

Volume Of Distribution ◽

Pharmacokinetic Parameters ◽

Maximum Plasma ◽

Elimination Half ◽

Liquid Chromatography Tandem Mass ◽

Stability Method ◽

Apparent Volume Of Distribution

Abstract Background: Buserelin is a LHRH agonist used for the treatment of hormone-dependent diseases in males and females. However, the pharmacokinetics of buserelin in pigs and cows are not clearly understood. This study was designed to develop a sensitive method to determine the concentration of buserelin and to investigate the pharmacokinetic parameters after intramuscular (i.m.) administration in pigs and cows. Results: A sensitive and rapid stability method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The pharmacokinetic parameters of buserelin after i.m. administration were studies in five pigs and five cows at a single dose of 1 mg per pig and 3 mg per cow. The plasma kinetics were analyzed by WinNonlin 8.1.0 software using a non-compartmental model. The mean concentration area under the curve (AUC0-t) was 25.02 ± 6.93 h·ng/mL for pigs and 5.63 ±1.86 h·ng/mL for cows. The maximum plasma concentration (Cmax) and time to reach the maximum concentration (tmax) were 10.99 ± 2.04 ng/mL and 0.57 ± 0.18 h for pigs and 2.68 ± 0.36 ng/mL and 1.05 ±0.27 h for cows, respectively. The apparent volume of distribution (Vz) in pigs and cows was 80.49 ± 43.88 L and 839.88 ± 174.77 L, respectively. The elimination half-time (t1/2λz), and clearance (CL) were 1.29 ± 0.40 h and 41.15 ± 11.18 L/h for pigs and 1.13 ± 0.3 h and 545.04 ± 166.40 L/h for cows, respectively. No adverse effects were observed in any of the animals. Conclusion: This study extends previous studies describing the pharmacokinetics of buserelin following i.m. administration in pigs and cows. Further studies investigating other factors were needed to establish therapeutic protocol in pigs and cows and to extrapolate these parameters to others economic animals.

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

Current Pharmaceutical Analysis ◽

10.2174/1573412916666200206143836 ◽

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.

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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

Current Pharmaceutical Analysis ◽

10.2174/1573412916666200130112247 ◽

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.

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

Drug Research ◽

10.1055/a-0885-1535 ◽

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%.

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Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method

Acta Pharmaceutica ◽

10.2478/acph-2021-0024 ◽

2021 ◽

Vol 71 (3) ◽

pp. 415-428

Author(s):

Sai-Jie Zuo ◽

Xiao-Liang Cheng ◽

Dong-Zheng Liu ◽

Wei-Yi Feng ◽

Yong-Xiao Cao ◽

...

Keyword(s):

Pharmacokinetic Study ◽

Growth Factor Receptor ◽

Internal Standard ◽

Gradient Elution ◽

Storage Conditions ◽

Rat Plasma ◽

Selected Reaction Monitoring ◽

Pharmacokinetic Parameters ◽

Egfr Inhibitor ◽

Reliable Quantification

Abstract1-(4-(Pyrrolidin-1-yl-methyl)phenyl)-3-(4-((3-(trifluoromethyl) phenyl)amino)quinazolin-6-yl)urea (ZCJ14), a novel epidermal growth factor receptor (EGFR) inhibitor, with diarylurea moiety, displays anticancer effect. In the present study, an LCMS/MS method was established to determine the concentration of ZCJ14 in rat plasma. Furthermore, the method was applied to investigate the pharmacokinetic characteristics of ZCJ14. Chromatographic separation of ZCJ14 and internal standard (IS) [1-phenyl-3-(4-((3-(trifluoromethyl)phenyl)amino) quinazolin-6-yl)urea] was accomplished by gradient elution using the Kromasil C18 column. The selected reaction monitoring transitions were performed at m/z 507.24→436.18 and 424.13→330.96 for ZCJ14 and IS, resp. The established method was linear over the concentration range of 10–1000 ng mL−1. The intra- and inter-day precisions were < 11.0 % (except for LLOQ which was up to 14.3 %) and the respective accuracies were within the range of 87.5–99.0 %. The extraction recovery and matrix effect were within the range of 88.4–104.5 % and 87.3–109.9 %, resp. ZCJ14 was stable under all storage conditions. The validated method was successfully applied to the pharmacokinetic study of ZCJ14 in rats, and the pharmacokinetic parameters have been determined. The oral bioavailability of ZCJ14 was found to be 46.1 %. Overall, this accurate and reliable quantification method might be useful for other diarylurea moiety-containing drugs.

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Simultaneous quantification of five bioactive 16-deoxybarringtogenol C triterpenoid saponins in rat plasma by HPLC-MS: Application to a pharmacokinetic study after oral administration of Xanthoceras sorbifolia Bunge husks extract

Acta Chromatographica ◽

10.1556/1326.2020.00834 ◽

2020 ◽

Author(s):

Weiwei Rong ◽

Zheng Sun ◽

Yina Guan ◽

Ran Liu ◽

Qing Li ◽

...

Keyword(s):

Oral Administration ◽

Pharmacokinetic Study ◽

Internal Standard ◽

Rat Plasma ◽

Pharmacokinetic Parameters ◽

Liquid Chromatography Mass Spectrometry ◽

Established Method ◽

Triterpenoid Saponins ◽

Terminal Half Life ◽

Insight Into

AbstractIn this study, a simple and rapid liquid chromatography-mass spectrometry method was developed to simultaneously determinate five 16-deoxybarringtogenol C triterpenoid saponins with the potential of neuroprotection in rat plasma following the oral administration of the Xanthoceras sorbifolia Bunge husks extract. With digoxin as the internal standard, the plasma samples were pre-treated by ethyl acetate-isopropanol (1:1, v/v). The chromatographic separation of the five analytes was performed using a Phenomenex C18 column (250 mm × 4.6 mm, 5.0 mm) with a mobile phase of 0.05% formic acid (A)-acetonitrile (B). The mass spectrometric detection was carried out in the selected ion mode in positive ionization. The extraction recoveries of the five analytes were all over 71.28%. The established method was fully validated in line with the ICH and Food and Drug Administration (FDA) guidelines and successfully applied to the pharmacokinetic study on the five analytes in rat plasma. The terminal half-life (t1/2) of the five analytes was 2.92 ± 0.57, 5.52 ± 1.75, 2.48 ± 0.62, 2.95 ± 0.94, and 2.34 ± 0.81, respectively. This study was purposed to investigate the oral pharmacokinetic parameters and gain an in-depth insight into the reasonable preclinical use of the husks extract derived from X. sorbifolia Bunge.

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UPLC-MS/MS Method for the Determination of 14 Compounds in Rat Plasma and Its Application in a Pharmacokinetic Study of Orally Administered Xiaoyao Powder

Molecules ◽

10.3390/molecules23102514 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2514 ◽

Cited By ~ 4

Author(s):

Mingyue Xu ◽

Zhanling Xu ◽

Qingxuan Xu ◽

Hongyue Zhang ◽

Mingyang Liu ◽

...

Keyword(s):

Pharmacokinetic Study ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Ultra Performance Liquid Chromatography ◽

Rat Plasma ◽

Chinese Herbs ◽

Tandem Mass ◽

Ionization Source ◽

Liquid Chromatography Tandem Mass ◽

Negative Ionization

Xiaoyao Powder (XYP), a common Chinese medicine, comprises eight traditional Chinese herbs and has been widely used clinically to treat liver damage and mental disorders. An ultra-performance liquid chromatography–tandem mass spectrometry method was developed to investigate the pharmacokinetics of 14 compounds (albiflorin, paeoniflorin, ferulic acid, senkyunolide I, quercetin, isoliquiritigenin, atractylenolide III, ligustilide, atractylenolide II, liquiritin, liquiritigenin, saikosaponin c, glycyrrhizic acid, and saikosaponin a) in XYP. Naringenin was used as the internal standard. The compounds were separated using an ACQUITY UPLCTM BEH C18 column (1.7 μm, 50 × 2.1 mm) with a mobile phase consisting of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring and an electrospray ionization source in both positive and negative ionization modes. All calibration curves exhibited good linearity (r2 > 0.9974) over the measured ranges. The intra- and inter-day precisions were within 12%, and the accuracy ranged from 89.93% to 106.64%. Extraction recovery and matrix effect results were satisfactory. The method was successfully applied in a pharmacokinetic study of the 14 compounds in rat plasma after the oral administration of XYP.

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