Pharmacokinetic and Bioavailability Studies of Galgravin after Oral and Intravenous Administration to Rats Using HPLC-MS/MS Method

This paper presents a new high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method with a rapid analysis of 6 min to determine the concentration of galgravin in rat plasma so as to study its pharmacokinetic features and bioavailability in vivo. Schisandrin was selected as the internal standard (IS). After extracting the analyte from plasma samples with ethyl acetate, methanol-H2O (0.1% formic acid) (85 : 15, v / v ) was used as mobile phase to achieve chromatographic separation on a C18 reversed phase column. The MS detection was performed in positive ion mode using electrospray ionization (ESI) source. This method showed good linearity over the range of 1~500 ng/mL ( R 2 > 0.999 ), and the lower limit of quantitation (LLOQ) was 1.0 ng/mL. The intraday precision and interday precision were both within 8.5%, whereas the accuracies were in the range of -2.6%–6.0%. The average recoveries of galgravin in rat plasma were between 92.3% and 99.3%. Moreover, galgravin was stable throughout storage and processing with all RSDs below 12.1%. After the successful application of this optimized method, the oral bioavailability of galgravin was determined to be 8.5%. This study will be helpful to the future research and development of galgravin.

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

Journal of Analytical Methods in Chemistry ◽

10.1155/2019/5163625 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 2

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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Simultaneous determination of calycosin, prim-O-glucosylcimifugin, and paeoniflorin in rat plasma by HPLC-MS/MS: application in the pharmacokinetic analysis of HQCF

Journal of International Medical Research ◽

10.1177/0300060520972902 ◽

2020 ◽

Vol 48 (11) ◽

pp. 030006052097290

Author(s):

Yulong Gu ◽

Xianglan Piao ◽

Dan Zhu

Keyword(s):

Formic Acid ◽

High Performance ◽

Internal Standard ◽

Gradient Elution ◽

Rat Plasma ◽

Selected Reaction Monitoring ◽

Pharmacokinetic Analysis ◽

Ionization Source ◽

Liquid Chromatography Tandem Mass

Objective This study aimed to develop and validate a high-performance liquid chromatography–tandem mass spectrometry method to simultaneously determine three bioactive components of the Huangqi Chifeng decoction (HQCF) in rat plasma. Methods Taxol was used as an internal standard in the developed method. Chromatographic separation was performed on a C18 column using a gradient elution with 0.1% formic acid in acetonitrile (v/v) and 0.1% formic acid in water (v/v) as the mobile phases at a flow rate of 0.4 mL·minute−1. All compounds were monitored via selected reaction monitoring with an electrospray ionization source. Results The lower limits of quantification of paeoniflorin, calycosin, and prim- O-glucosylcimifugin were 15.0, 0.75, and 0.75 ng·mL−1, respectively. The calibration curves indicated optimal linearity ( r > 0.99) across the concentration ranges. The specificity, precision, accuracy, recovery, matrix effect, and stability of the method were validated. This method was successfully applied in a pharmacokinetics study of the three compounds in rat plasma. Conclusion The pharmacokinetics results provide insights into the mechanisms of HQCF in vivo and its future clinical application.

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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

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18094624 ◽

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.

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Pharmacokinetic Comparison of Isoalantolactone and Alantolactone in Rats after Administration Separately by Optimization of an UPLC-MS2Method

Journal of Chemistry ◽

10.1155/2014/354618 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Renjie Xu ◽

Mengyue Wang ◽

Ying Peng ◽

Xiaobo Li

Keyword(s):

Multiple Reaction Monitoring ◽

Internal Standard ◽

Rat Plasma ◽

Sprague Dawley ◽

Ionization Source ◽

Fragment Ions ◽

Sprague Dawley Rats ◽

Liquid Chromatography Tandem Mass ◽

Positive Ion

Isoalantolactone and alantolactone are two major active ingredients that are present in many medicinal plants. In this study, a sensitive and rapid ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for determination of the two compounds in rat plasma, separately. In this method, an electrospray ionization source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) was selected for quantification using target fragment ions 233.2→187.1 for isoalantolactone (alantolactone) and 245.1→189.1 for internal standard (IS). Retention time of the lactones and IS was within 3.0 min. Further calibration suggested a linear regression can be calculated within 2.5–500 ng/mL for isoalantolactone and 4–500 ng/mL for alantolactone. This method was used to compare the pharmacokinetic characteristics of isoalantolactone and alantolactone at a single dose of 5 mg/kg into male Sprague-Dawley rats by intravenous administration separately. The levels oft1/2, Kel, CL,Cmax, and AUC were significantly increased in the alantolactone group compared to isoalantolactone. These results suggested that isoalantolactone was distributed and eliminated more rapidly than alantolactone in rats when administered, respectively.

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Simultaneous determination and pharmacokinetics studies of five isoflavones in rat plasma by UHPLC-MS/MS after oral administration of Radix Astragali extract

Acta Chromatographica ◽

10.1556/1326.2020.00845 ◽

2021 ◽

Author(s):

Jianwei Han ◽

Wenbo Zhu ◽

Ling Yu ◽

Yajun Chen ◽

Gaosong Wu ◽

...

Keyword(s):

Oral Administration ◽

High Performance ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Rat Plasma ◽

Tandem Mass ◽

Radix Astragali ◽

Limit Of Quantification ◽

Liquid Chromatography Tandem Mass ◽

Mass Spectrometery

AbstractA rapid, sensitive and convenient method based on ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was developed and validated for the simultaneous quantification of calycosin-7-O-β-d-glucoside (CCSG), ononin, calycosin, (6aR,11aR)-9,10-dimethoxypterocarpan-3-O-β-d-glucopyanoside (DPPG), and 7,2′-dihydroxy-3′,4′-dimethoxyisoflavan-7-O-β-d-glucopyanoside (DIFG) in rat plasma after oral administration of the methanol extraction from Radix Astragali. Theophylline played the role of internal standard (IS). Preparation of plasma samples by liquid-liquid extraction method with ethyl acetate after precipitation of protein with methanol. The analytes were detected with a triple quadrupole tandem mass spectrometery (MS) in multiple reaction monitoring (MRM) mode and a positive ion electrospray ionization (ESI). The method was validated with the concentration ranges of 1.96–62.69 ng/mL for CCSG, 1.70–54.5 ng/mL for ononin, 1.85–59.06 ng/mL for calycosin, 2.14–137.24 ng/mL for DPPG and1.96–125.25 ng/mL for DIFG, respectively. The method had the lower limit of quantification (LLOQ) with 0.49, 0.21, 0.92, 1.07, and 0.98 ng/mL for CCSG, ononin, calycosin, DPPG and DIFG respectively, and the precision less than 10%. The RSD of the accuracy was in the range of −4.35–8.91%. The results may be helpful to provide more accurate references to clinical application of this herb.

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

BioMed Research International ◽

10.1155/2021/9953664 ◽

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.

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DEVELOPMENT AND VALIDATION OF NEW RP–HPLC METHOD FOR DETERMINATION OF BESIFLOXACIN IN ANIMAL MODEL

INDIAN DRUGS ◽

10.53879/id.52.01.10228 ◽

2015 ◽

Vol 52 (01) ◽

pp. 26-32

Author(s):

A Singh ◽

◽

C. L Singh ◽

S. Kumar ◽

M. Kumar

Keyword(s):

High Performance ◽

Internal Standard ◽

Rat Plasma ◽

Reversed Phase ◽

Hplc Method ◽

Standard Curve ◽

Absorbance Detection ◽

Rp Hplc ◽

Ich Guidelines ◽

Development And Validation

A sensitive and accurate reversed– phase high performance liquid chromatography (RP-HPLC) method with UV absorbance detection at 289 nm was developed and validated for the determination and quantification of besifloxacin (BSF) in rat plasma. Ofloxacin was used as an internal standard (IS). The sample was prepared by liquid extraction of BSF from plasma, using methanol and acetonitrile (70:30). The chromatographic separation was achieved with octadecylsilane (ODS-3), Hypersil® C18 column (250 mm×6mm×5μm). The chromatographic runtime was less than 5 minutes where the retention time of internal standard and the drug was 2.15 min and 3.30 min respectively. A standard curve with a regression coefficient (r2) 0.999 was obtained in the range of 0.025-20 μg/mL. The method was validated with respect to linearity, range, precision, accuracy and robustness according to ICH guidelines. The method was found to be accurate and robust with a runtime of less than 5 minutes. Hence, the present method was rapid and economical to use for clinical studies as well as to analyze the drug in different plasma samples.

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A Novel LC-MS Method for the Determination of Abiraterone in Rat Plasma and its Application to Pharmacokinetic Studies

Current Pharmaceutical Analysis ◽

10.2174/2213337208666210816112837 ◽

2021 ◽

Vol 17 ◽

Author(s):

Linzhi Dai ◽

Pei Lv ◽

Yun He ◽

Xiaoli Wang ◽

Lili Chen ◽

...

Keyword(s):

Liquid Chromatography ◽

Mobile Phase ◽

High Performance ◽

Analytical Procedure ◽

Internal Standard ◽

Rat Plasma ◽

Pharmacokinetic Studies ◽

Quadrupole Mass ◽

Limit Of Quantitation

Background: High–performance liquid chromatography (HPLC)–ultraviolet (UV) and liquid chromatography (LC)–mass spectrometry (MS)/MS methods have been used to analyse abiraterone (ART); however, a single-quadrupole mass spectrometer with LC-MS systems has never been used to analyse ART. Objective: The study aimed to establish a novel, simple assay of quantitating ART in rat plasma through LC–MS. Method: The analytical procedure involved the extraction of ART and D4-ART (internal standard, IS) from rat plasma through simple protein precipitation. Chromatographic separation was achieved using an isocratic mobile phase (acetonitrile: 5 mM ammonium formate with 0.1% formic acid, 50:50 v/v) at a flow rate of 0.30 mL/min on a Waters XBridge® C18 column with a total run time of 5 min. LC–MS ion transitions monitored were 350.1 and 354.1 for ART and IS, respectively. The method was validated, and the results met acceptance criteria. Results: The lower limit of quantitation achieved was 1 ng/mL, and linearity was 1–8000 ng/mL. The intra- and inter-day precisions were 1.26%–14.20% and 5.49%–13.08%, respectively, in rat plasma.

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Simultaneous Determination and Pharmacokinetics Study of Six Triterpenes in Rat Plasma by UHPLC-MS/MS after Oral Administration of Sanguisorba officinalis L. Extract

Molecules ◽

10.3390/molecules23112980 ◽

2018 ◽

Vol 23 (11) ◽

pp. 2980 ◽

Cited By ~ 4

Author(s):

Chengcui Wu ◽

Meicun Yao ◽

Wa Li ◽

Binbin Cui ◽

Hongrui Dong ◽

...

Keyword(s):

Oral Administration ◽

High Performance ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Current Method ◽

Rat Plasma ◽

Ion Source ◽

Pharmacokinetics Study ◽

Liquid Chromatography Tandem Mass ◽

Sanguisorba Officinalis

A selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of ziyuglycoside I (I), 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester (II), 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester (III), rosamultin (IV), 1β-hydroxyeuscaphic acid (V) and alpinoside (VI) in rats after oral administration of Sanguisorba officinalis L. (S. officinalis) extract. The 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester, rosamultin, 1β-hydroxyeuscaphic acid and alpinoside in rat plasma were the first report in the pharmacokinetics study in the present study. The analytes were quantified using the multiple reaction monitoring (MRM) mode with the electrospray ion source in positive electrospray ionization. Plasma was extracted with ethyl acetate via liquid–liquid extraction. Bifendate was used as internal standard (IS). The current method was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability. The lower limits of quantification of ziyuglycoside I, 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester, rosamultin, 1β-hydroxyeuscaphic acid and alpinoside were 6.1, 4.9, 1.3, 3.8, 1.5 and 5.7 ng/mL, respectively. Intra-day and inter-day precision and the accuracy of the assay were in range from −9.48 to 12.74%. The extraction recoveries of analytes and bifendate (IS) from rat plasma ranged from 77.17% to 92.48%. Six compounds could be rapidly absorbed into blood (Tmax, 0.58–1.58 h), and then eliminated relatively slowly (t1/2, 6.86–11.63 h). The pharmacokinetic results might contribute to further guide the clinical application of S. officinalis.

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Determination of Fenofibric Acid in Rat Plasma and its Application to a Comparative Pharmacokinetic Study of JW322 and Fenofibrate

Drug Research ◽

10.1055/s-0043-109243 ◽

2017 ◽

Vol 67 (09) ◽

pp. 534-538

Author(s):

Tae Kim

Keyword(s):

High Performance ◽

Internal Standard ◽

Relative Bioavailability ◽

Rat Plasma ◽

Reversed Phase ◽

Pharmacokinetic Parameters ◽

Fenofibric Acid ◽

Ultraviolet Detector ◽

Quantitation Limit

AbstractIn this study, a sensitive and reliable method for the quantitation of fenofibric acid in rat plasma was developed and validated using high performance liquid chromatography (HPLC). The plasma samples were prepared by deproteinization, and sildenafil was used as an internal standard. Chromatographic separation was achieved using a reversed-phase (C18) column. The mobile phase, 0.02 M ammonium acetate buffer:acetonitrile (35:65, v/v), was run at a flow rate of 1.0 mL/min, and the column eluent was monitored using an ultraviolet detector at 280 nm at room temperature. The retention times of sildenafil (an internal standard), and fenofibric acid were approximately 5.9 and 7.7 min, respectively. The quantitation limit of fenofibric acid in rat plasma was 0.03 μg/mL. Pharmacokinetic parameters of fenofibric acid was evaluated after oral (at doses of 20 mg/kg) administration of JW322 and fenofibrate in rats. After oral administration (20 mg/kg) of JW322, relative bioavailability was approximately 272.8% compared to fenofibrate.

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