Pharmacokinetic Comparisons of Mangiferin and Mangiferin Monosodium Salt in Rat Plasma by UPLC-MS/MS

Mangiferin (MG) is an active component in natural medicines, and various studies have been reported on pharmacological effects, but the low solubility and bioavailability of MG limit its wide application. The aim of the present study was to investigate the pharmacokinetic profiles of mangiferin (MG) and mangiferin monosodium salt (MG-Na) in rat plasma by UPLC-MS/MS, which were then compared between the two groups. An appropriate high sensitivity and selectivity ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was applied to the comparison of plasma pharmacokinetics in MG and MG-Na using carbamazepine as internal standard (IS). These results showed that there were statistically significant differences in the pharmacokinetic parameters between MG and MG-Na after a single oral administration at 100 mg/kg. When compared with pharmacokinetic parameters of MG, the AUC(0-t), AUC(0–∞), Cmax,K10, and Ka of MG-Na were increased by 5.6-, 5.7-, 20.8-, 8-, and 83.6-fold, while the Tmax and CL/F were decreased by 4- and 5.7-fold (P<0.001), respectively. t1/2 value showed an increasing trend, but was statistically significant between the two groups. Moreover, the AUC value in the MG-Na group was significantly increased and the relative bioavailability was calculated to be 570% when compared with that of the MG group. These results suggested that the salification reaction of MG can effectively enhance gastrointestinal absorption and relative bioavailability by improving solubility and membrane permeability.

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Liquid Chromatography Tandem Mass Spectrometric Analytical Method for Study of Colchicine in Rats Given Low Doses

Processes ◽

10.3390/pr9112007 ◽

2021 ◽

Vol 9 (11) ◽

pp. 2007

Author(s):

Hamdah M. Al Nebaihi ◽

Tyson S. Le ◽

Neal M. Davies ◽

Dion R. Brocks

Keyword(s):

Whole Blood ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Rat Plasma ◽

Low Doses ◽

Blood Concentrations ◽

Liquid Chromatography Tandem Mass ◽

Sensitivity And Selectivity ◽

Tandem Mass Spectrometric ◽

Lower Limits

A selective and sensitive assay was developed for colchicine in rat specimens. Colchicine and its deuterated analog (as internal standard, IS) were extracted from rat specimens (minimal 0.1 mL plasma, whole blood, or urine) using liquid-liquid extraction with n-hexane:dichloromethane:isopropanol. The mobile phase (formic acid: ammonium acetate: methanol) was pumped with uniform flow through an octadecylsilane analytical column. Detection was carried out by electrospray positive ionization in the multiple-reaction monitoring mode. The assay (total run time <3 min) had excellent linearity over a wide (400–800-fold) concentration range. The mean absolute recovery was >96.8%. The intra- and inter-day coefficients of variation were ˂15%, with lower limits of quantitation of 0.5 ng/mL in 0.1 mL of rat plasma. The method also provided the same lower limits of quantitation in urine and whole blood with 0.1 mL volumes, and 0.1 ng/mL using 0.5 mL of rat plasma. The blood-to-plasma ratio was >1. Rats had measurable colchicine blood concentrations for at least 24 h after intravenous doses of 0.1 mg/kg. The method possessed suitable measures of sensitivity and selectivity for detecting colchicine in several specimen types in rats given low doses.

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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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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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Simultaneous Determination of Columbianadin and Its Metabolite Columbianetin in Rat Plasma by LC-MS/MS: Application to Pharmacokinetics of Columbianadin after Oral Administration

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/8568303 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Jin Li ◽

Zhen Li ◽

Qian Luo ◽

Chun-Peng Wang ◽

Jun He ◽

...

Keyword(s):

Oral Administration ◽

Internal Standard ◽

Rat Plasma ◽

Pharmacokinetic Parameters ◽

Antitumor Activities ◽

Limit Of Quantification ◽

Potential Development ◽

Liquid Chromatography Tandem Mass ◽

Acetate Aqueous Solution

Columbianadin and its metabolite columbianetin exhibited the anti-inflammatory, analgesic, calcium channel blocking and antitumor activities. To compare the differences between pharmacokinetics of columbianadin and its metabolite columbianetin after oral administration of pure columbianadin and Angelicae Pubescentis Radix (APR) extract, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated to simultaneously determine columbianadin and columbianetin in rat plasma. Two analytes and an internal standard (warfarin) were well separated and determined after liquid-liquid extraction with ethyl acetate. Ammonium acetate aqueous solution (1 mmol/L) and acetonitrile were used as the mobile phase and the flow rate was 0.3 mL/min. The lower limit of quantification (LLOQ) was 0.1 ng/mL for columbianetin and 0.5 ng/mL for columbianadin, respectively. There were significant differences between some pharmacokinetic parameters and bioavailability of columbianadin after oral administration of pure columbianadin and APR extract. The studies on comparative pharmacokinetics of columbianadin were of great use for facilitating the clinical application of columbianadin and were also highly meaningful for the potential development of APR.

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Revealing changes in curcumin bioavailability using vitamin C as an enhancer by HPLC-MS/MS

Current Pharmaceutical Analysis ◽

10.2174/1573412916666191220150039 ◽

2019 ◽

Vol 16 ◽

Author(s):

Xufen Dai ◽

Jiaxue Hao ◽

Ying Feng ◽

Jing Wang ◽

Qiannan Li ◽

...

Keyword(s):

Vitamin C ◽

High Performance ◽

Internal Standard ◽

Fold Increase ◽

Rat Plasma ◽

Pharmacokinetic Parameters ◽

Solution Ph ◽

Esi Ms ◽

Simple Strategy ◽

Isolated Compound

Background: Curcumin (CUR), a natural isolated compound from turmeric, has been the promising star in fighting many diseases but the broad application of curcumin has been limited ascribed to low bioavailability. Objective: The aim of this study is to pursue the enhancement of curcumin bioavailability through co-administration of vitamin C. Methods: Such purpose was achieved through the analysis of curcumin pharmacokinetics by high performance liquid chromatography coupled with electrospray ionization - tandem mass spectrometry (HPLC - ESI - MS/MS). The plasma was separated on a C18 reverse phase column using acetonitrile and ammonium formate solution (pH 6.5; 2.0 mM) at 0.8 mL/min. MS/MS detection was carried out in negative mode using mass patterns of m/z 367.0 > 216.7 for curcumin and m/z 265.2 > 223.9 for internal standard (honokiol). Results: Successful application of the proposed method in the pharmacokinetic study presented clear changes in key pharmacokinetic parameters including the growth of AUC (0-t) up to 2.4 times, 2.2-fold increase of Cmax, 2.2-fold loss of CL, and 1.5-fold diminishment of t1/2. Conclusion: We developed an HPLC-ESI-MS/MS method for determination of curcumin in rat plasma and validated the improvement of bioavailability of curcumin through co-administration of vitamin C. We reasoned these changes to the inhibition of lipid peroxidation induced by the use of vitamin C. Such a simple strategy is possible to become an alternative for enhancing curcumin efficiency in practice.

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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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Liquid Chromatography-Tandem Mass Spectrometry of Desoxo-Narchinol a and Its Pharmacokinetics and Oral Bioavailability in Rats and Mice

Molecules ◽

10.3390/molecules24112037 ◽

2019 ◽

Vol 24 (11) ◽

pp. 2037 ◽

Cited By ~ 2

Author(s):

Subindra Kazi Thapa ◽

Mahesh Upadhyay ◽

Tae Hwan Kim ◽

Soyoung Shin ◽

Sung-Joo Park ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Oral Bioavailability ◽

Internal Standard ◽

Rat Plasma ◽

Tandem Mass ◽

Mouse Plasma ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass

Desoxo-narchinol A is one of the major active constituents from Nardostachys jatamansi, which has been reported to possess various pharmacological activities, including anti-inflammatory, antioxidant, and anticonvulsant activity. A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of desoxo-narchinol A in two different biological matrices, i.e., rat plasma and mouse plasma, using sildenafil as an internal standard (IS). The method involved simple protein precipitation with acetonitrile and the analyte was separated by gradient elution using 100% acetonitrile and 0.1% formic acid in water as a mobile phase. The MS detection was performed with a turbo electrospray in positive ion mode. The lower limit of quantification was 10 ng/mL in both rat and mouse plasma. Intra- and inter-day accuracies were in the ranges of 97.23–104.54% in the rat plasma and 95.90–110.11% in the mouse plasma. The precisions were within 8.65% and 6.46% in the rat and mouse plasma, respectively. The method was applied to examine the pharmacokinetics of desoxo-narchinol A, and the oral bioavailability of desoxo-narchinol A was 18.1% in rats and 28.4% in mice. The present results may be useful for further preclinical and clinical studies of desoxo-narchinol A.

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Simultaneous determination of Rivaroxaban and TAK-438 in rat plasma by LC–MS/MS: application to pharmacokinetic interaction study

Bioanalysis ◽

10.4155/bio-2019-0130 ◽

2020 ◽

Vol 12 (1) ◽

pp. 11-22 ◽

Cited By ~ 4

Author(s):

Libin Wang ◽

Shouchang Gai ◽

Xiaorui Zhang ◽

Xiaohui Xu ◽

Nan Gou ◽

...

Keyword(s):

Drug Interactions ◽

Internal Standard ◽

Pharmacokinetic Interaction ◽

Rat Plasma ◽

Pharmacokinetic Parameters ◽

Interaction Study ◽

Significant Difference ◽

Us Fda ◽

First Time

Aim: A sensitive and reliable LC–MS/MS method has been established and validated to the quantitation of rivaroxaban (RIV) and TAK-438 in rat plasma using carbamazepine as internal standard. Results: The procedure of method validation was conducted according to the guidelines of EMA and US FDA. At the same time, the method was applied to pharmacokinetic interactions study between RIV and TAK-438 for the first time. When RIV and TAK-438 co-administration to rats, main pharmacokinetic parameters of TAK-438 like AUC(0-t), AUC(0-∞) and Cmax had statistically significant increase. The main pharmacokinetic parameters of RIV have no statistically significant difference (p > 0.05) when co-administered except for t1/2 (p < 0.01). Conclusion: The results indicated that drug–drug interactions occurred between RIV and TAK-438 when co-administered to rats.

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Simultaneous Determination and Pharmacokinetic Characterization of Glycyrrhizin, Isoliquiritigenin, Liquiritigenin, and Liquiritin in Rat Plasma Following Oral Administration of Glycyrrhizae Radix Extract

Molecules ◽

10.3390/molecules24091816 ◽

2019 ◽

Vol 24 (9) ◽

pp. 1816 ◽

Cited By ~ 4

Author(s):

You Jin Han ◽

Bitna Kang ◽

Eun-Ju Yang ◽

Min-Koo Choi ◽

Im-Sook Song

Keyword(s):

Oral Administration ◽

Analytical Method ◽

Plasma Concentrations ◽

Rat Plasma ◽

Pharmacokinetic Studies ◽

Elution Time ◽

Glycyrrhizae Radix ◽

Single Oral Administration ◽

Limit Of Quantitation ◽

Liquid Chromatography Tandem Mass

Glycyrrhizae Radix is widely used as herbal medicine and is effective against inflammation, various cancers, and digestive disorders. We aimed to develop a sensitive and simultaneous analytical method for detecting glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin, the four marker components of Glycyrrhizae Radix extract (GRE), in rat plasma using liquid chromatography-tandem mass spectrometry and to apply this analytical method to pharmacokinetic studies. Retention times for glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin were 7.8 min, 4.1 min, 3.1 min, and 2.0 min, respectively, suggesting that the four analytes were well separated without any interfering peaks around the peak elution time. The lower limit of quantitation was 2 ng/mL for glycyrrhizin and 0.2 ng/mL for isoliquiritigenin, liquiritigenin, and liquiritin; the inter- and intra-day accuracy, precision, and stability were less than 15%. Plasma concentrations of glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin were quantified for 24 h after a single oral administration of 1 g/kg GRE to four rats. Among the four components, plasma concentration of glycyrrhizin was the highest and exhibited a long half-life (23.1 ± 15.5 h). Interestingly, plasma concentrations of isoliquiritigenin and liquiritigenin were restored to the initial concentration at 4–10 h after the GRE administration, as evidenced by liquiritin biotransformation into isoliquiritigenin and liquiritigenin, catalyzed by fecal lysate and gut wall enzymes. In conclusion, our analytical method developed for detecting glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin could be successfully applied to investigate their pharmacokinetic properties in rats and would be useful for conducting further studies on the efficacy, toxicity, and biopharmaceutics of GREs and their marker components.

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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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