Comparative Pharmacokinetics of Geniposidic Acid, Genipin-1-β-Gentiobioside, Geniposide, Genipin, and Crocetin in Rats after Oral Administration of Crude Gardeniae Fructus and Its Three Processed Products Using LC-MS/MS

The extract of Gardeniae Fructus (GF) with different processing methods processed the different medicinal properties and efficacy. Crude GF (CGF) could be processed into stir-frying GF (SGF), gancao mix-frying GF (GCGF), and ginger mix-frying GF (GIGF) in practice. An LC-MS/MS method was established for simultaneous quantification of geniposidic acid, geniposide, genipin-1-β-gentiobioside, genipin, and crocetin in the rat plasma. The LLOQs for determination of all five components were 10 ng/mL. The accuracies of intraday and interday were in the range of 91%–105%. The recoveries of 5 analytes ranged from 81.0% to 114% with RSD less than 14%. The results showed that the AUCs (area under the plasma concentration-time curve) and Cmax (maximum plasma concentration) of geniposidic acid, genipin-1-β-gentiobioside, and geniposide after oral administration of the CGF extract were apparently higher than those after oral administration of other processed extracts. Cmax of geniposide in plasma after administration of GIGF significantly decreased (p<0.01). Genipin was not detected in rat plasma after administration of the GIGF extract, but it can be detected in plasma after administration of CGF, SGF, and GCGF extract. Furthermore, crocin I and crocin II were not detected in plasma samples. Crocetin had higher concentration in rat plasma versus lower contents in extract. It was demonstrated that the different processing methods might influence the pharmacokinetics of geniposidic acid, genipin-1-β-gentiobioside, geniposide, genipin, and crocetin.

Download Full-text

Simultaneous Determination and Pharmacokinetic Study of Quercetin, Luteolin, and Apigenin in Rat Plasma after Oral Administration of Matricaria chamomilla L. Extract by HPLC-UV

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/8370584 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Xiaoxv Dong ◽

Wei Lan ◽

Xingbin Yin ◽

Chunjing Yang ◽

Wenping Wang ◽

...

Keyword(s):

Plasma Concentration ◽

Oral Administration ◽

Simultaneous Determination ◽

Rat Plasma ◽

Maximum Plasma Concentration ◽

Maximum Plasma ◽

Matricaria Chamomilla ◽

The Mean ◽

Lower Limits

A simple and sensitive HPLC-UV method has been developed for the simultaneous determination of quercetin, luteolin, and apigenin in rat plasma after oral administration of Matricaria chamomilla L. extract. The flow rate was set at 1.0 ml/min and the detection wavelength was kept at 350 nm. The calibration curves were linear in the range of 0.11–11.36 μg/ml for quercetin, 0.11–11.20 μg/ml for luteolin, and 0.11–10.60 μg/ml for apigenin, respectively. The intraday and interday precisions (RSD) were less than 8.32 and 8.81%, respectively. The lower limits of quantification (LLOQ) of the three compounds were 0.11 μg/ml. The mean recoveries for quercetin, luteolin, and apigenin were 99.11, 95.62, and 95.21%, respectively. Stability studies demonstrated that the three compounds were stable in the preparation and analytical process. The maximum plasma concentration (Cmax) was 0.29 ± 0.06, 3.04 ± 0.60, and 0.42 ± 0.10 μg/ml, respectively. The time to reach the maximum plasma concentration (Tmax) was 0.79 ± 0.25, 0.42 ± 0.09, and 0.51 ± 0.13 h, respectively. The validated method was successfully applied to investigate the pharmacokinetics study of quercetin, luteolin, and apigenin in rat plasma after oral administration of M. chamomilla extract.

Download Full-text

Pharmacokinetic Comparisons of Different Combinations of Yigan Jiangzhi Formula in Rats: Simultaneous Determination of Fourteen Components by UPLC-MS/MS

Journal of Analytical Methods in Chemistry ◽

10.1155/2020/9353975 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Yang Wang ◽

Ping Wang ◽

Jun Xie ◽

Zhaorui Yin ◽

Xiaoyan Lin ◽

...

Keyword(s):

Plasma Concentration ◽

Simultaneous Determination ◽

Dose Group ◽

Drug Prescription ◽

Rat Plasma ◽

High Dose ◽

Maximum Plasma ◽

Concentration Time ◽

Limit Of Quantitation

A rapid, specific, and sensitive analysis for simultaneous determination of fourteen components (daidzein, fermononetin, apigenin, luteolin, puerarin, ononin, calycosin-7-O-β-D-glucoside, tanshinol, rosmarinic acid, alkanoic acid, salvianolic acid B, berberine, jatrorrhizin, and palmatine) of Yigan Jiangzhi formula (YGJZF, a clinical experienced formula for damp-heat syndrome) in rat plasma was developed and validated using ultraperformance liquid chromatography coupled with mass spectrometry. Lower limit of quantitation ranged from 0.2–10.0 ng/mL, and the calibration curves showed good linearity over 500 times of measuring range. The validated method was successfully applied to the pharmacokinetics investigation of the fourteen compounds in rat plasma after oral administration of two different doses of YGJZF. Compared with the low-dose group of YGJZF, the high-dose group showed significant increase (P<0.01 or P<0.05) in maximum plasma concentration, maximum concentration time, and area under the plasma concentration-time curve and decrease (P<0.01 or P<0.05) in clearance of most of the fourteen analytes, which suggested that the bioavailability of these components could be enhanced by increasing dosage. The above results may provide useful information for cognizing the relationship between in vitro and in vivo data of the fourteen bioactive ingredients of YGJZF and further guiding rational clinical drug prescription.

Download Full-text

The Determination of 10 Compounds of GuiZhi Decoction in Rat Plasma after Oral Administration by HPLC-MS/MS and its Application to a Pharmacokinetic Study

10.21203/rs.3.rs-254154/v1 ◽

2021 ◽

Author(s):

Huan Gao ◽

Qin Guo ◽

Lishi Zhang ◽

Jiannan Song ◽

Dong Bai ◽

...

Keyword(s):

Plasma Concentration ◽

Oral Administration ◽

Lower Limit ◽

Intravenous Injection ◽

Pharmacokinetic Study ◽

Rat Plasma ◽

Glycyrrhetinic Acid ◽

Concentration Time ◽

Guizhi Decoction

Abstract Background: Guizhi Decoction (GZD), a traditional Chinese medical formula, has been commonly used to treat fever, sweating, and cold in China. Methods: The high performance liquid chromatography -tandem mass spectrometry ( HPLC-MS/MS ) method was established for the determination of 10 compounds, including cinnamic acid , paeoniflorin, albiflorin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, and 6-gingerol. And the specificity, linearity, lower limit of quantification (LLOQ), lower limit of detection (LLOD), precision and accuracy, recovery, matrix effect, and stability were used to verify the HPLC-MS/MS method. This validated method was successfully applied for pharmacokinetic study of the 10 compounds in rat plasma after oral administration of GZD in three doses (40 g crude drug·kg −1 , 20 g crude drug·kg −1 , 10 g crude drug·kg −1 ) and intravenous injection of GZD extraction at a dose of 2.0 g crude drug·kg −1 .The measurements of pharmacokinetic parameters including AUC 0–∞ , T 1/2 , T max , C max , Vz_F, Cl_F, and MRT, were performed using a non-compartmental model with Winnonlin 8.1 software. Results: The results showed that 10 compounds were detected in plasma after oral administration of GZD. the compounds (except for glycyrrhetinic acid) reached the maximum blood concentration quickly, whose Tmax was about 0.1-0.2 min. And a total of 9 compounds were detected after intravenous injection of GZD. The plasma concentration-time curve of these compounds declines rapidly at the beginning, and then decreased slowly, indicating that the plasma concentration-time curves were double exponential function curves. Conclusions: In this study, the developed method was suitable for pharmacokinetic analysis of the main compounds of GZD in rat plasma, and may reveal the pharmacodynamic material basis of GZD and provide a reference for the rational use of GZD in the clinic.

Download Full-text

Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS

Molecules ◽

10.3390/molecules24010071 ◽

2018 ◽

Vol 24 (1) ◽

pp. 71 ◽

Cited By ~ 1

Author(s):

Yu-Feng Yao ◽

Chao-Zhan Lin ◽

Fang-Le Liu ◽

Run-Jing Zhang ◽

Qiu-Yu Zhang ◽

...

Keyword(s):

Oral Administration ◽

Degradation Products ◽

Plasma Concentrations ◽

Rat Plasma ◽

Pharmacokinetic Analysis ◽

Pharmacokinetic Studies ◽

Maximum Plasma ◽

Time Curve ◽

Tof Ms

The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites—rhamnocitrin 3-O-β-glc and rhamnocitrin—in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites—rhamnocitrin—was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability.

Download Full-text

DETERMINATION AND VALIDATION OF NARINGIN IN RAT PLASMA BY RP-HPLC

INDIAN DRUGS ◽

10.53879/id.52.07.10130 ◽

2015 ◽

Vol 52 (07) ◽

pp. 29-32

Author(s):

S Venkatesh ◽

◽

B. Pagilla ◽

B. M. Reddy ◽

R. Mullangi

Keyword(s):

Quality Control ◽

Plasma Concentration ◽

Rat Plasma ◽

Organic Layer ◽

Maximum Plasma ◽

Simple Liquid ◽

Rp Hplc ◽

Relative Standard ◽

Control Samples

A simple, accurate isocratic reverse phase high performance liquid chromatography (RP-HPLC) method was developed for the determination of the plasma concentration of naringin, a flavanone glycoside in rat plasma. An assay procedure involved simple liquid–liquid extraction of naringin from plasma directly into methanol. The organic layer was separated, filtered and injected onto a Phenomenex-C18 column (4.6 × 250 mm, 5 μm). The mobile phase acetonitrile and water (30:70, V/V) was used at a flow rate of 1.0 mL/min for the effective separation of naringin. The detection of the analyte peak was achieved by monitoring the eluate using a UV detector at 283 nm. The peak area of analyte was used for quantification of plasma samples. The retention time of naringin was 4.7 min. The standard curve for naringin was linear (r2 = 0.9987) in the concentration range 100-2000 ng/mL. The absolute recoveries of naringin were in the range 85–115% from rat plasma. The lower limit of quantification (LLOQ) of naringin was 30 ng/mL. The intra and inter-assay precisions in the measurement of quality control samples of 100, 400, 900 and 1600 ng/mL, were in the range of 0.19-5.44% and 0.27-2.35% relative standard deviation (RSD), respectively. Accuracy in the measurement of quality control samples was in the range 98.40-107.9% of the spiked nominal values. The plasma concentration of naringin was increased with increase in test dose levels. From the results, maximum plasma concentration of naringin was found to be 289.03 and 757.3 ng/mL with 15 and 30 mg/kg, oral doses, respectively at 2 h. This method is simple and helps in determination of naringin in rat plasma.

Download Full-text

Simultaneous Determination of Aesculin, Aesculetin, Fraxetin, Fraxin and Polydatin in Beagle Dog Plasma by UPLC-ESI-MS/MS and Its Application in a Pharmacokinetic Study after Oral Administration Extracts of Ledum palustre L.

Molecules ◽

10.3390/molecules23092285 ◽

2018 ◽

Vol 23 (9) ◽

pp. 2285 ◽

Cited By ~ 4

Author(s):

Zhibin Wang ◽

Wenbo Zhu ◽

Hua Liu ◽

Gaosong Wu ◽

Mengmeng Song ◽

...

Keyword(s):

Plasma Concentration ◽

Oral Administration ◽

Simultaneous Determination ◽

Maximum Plasma Concentration ◽

Maximum Plasma ◽

Beagle Dog ◽

Esi Ms ◽

Ledum Palustre ◽

Dog Plasma

A rapid, simple and sensitive ultra-performance liquid chromatography-electrospray-ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and validated for the simultaneous determination of aesculin, aesculetin, fraxetin, fraxin and polydatin in beagle dog plasma for the first time. Plasma samples were pretreated by protein precipitation with methanol. Chromatographic separation was performed on an Acquity UPLC HSS T3 C18 column (2.1 mm × 100 mm, 1.8 μm) with gradient elution at a flow rate of 0.4 mL/min, using a mobile phase consisting of 0.1% formic acid (A) and acetonitrile (B). The analytes and IS were detected by multiple reaction monitoring (MRM) via negative ion mode with ion transitions of m/z 339.1–m/z 176.8 for aesculin, m/z 176.8–m/z 88.9 for aesculetin, m/z 206.8–m/z 192.1 for fraxetin, m/z 369.1–m/z 206.9 for fraxin, m/z 389.1–m/z 227.0 for polydatin and m/z 415.2–m/z 295.1 for puerarin. This method was validated according to the FDA guidelines and the results met the requirements of analysis. The calibration curves of analytes were linear with correlation coefficients more than 0.9980. The intra- and inter-day precisions were less than 15% and the accuracy was within ±15%. The maximum plasma concentration (Cmax) of aesculin, aesculetin, fraxetin, fraxin and polydatin was 46.75 ± 7.46, 209.9 ± 57.65, 369.7 ± 48.87, 67.04 ± 12.09 and 47.14 ± 12.04 ng/mL, respectively. The time to reach the maximum plasma concentration (Tmax) was 1.32 ± 0.38 h for aesculin, 1.03 ± 0.27 h for aesculetin, 0.94 ± 0.23 h for fraxetin, 0.83 ± 0.18 h for fraxin and 1.15 ± 0.15 h for polydatin. The results indicated that the absorption of aesculin might be slow in beagle dog plasma. This method was successfully applied for pharmacokinetics in beagle dog plasma after oral administration of the extracts of Ledum palustre L. at a dosage of 0.27 g/kg.

Download Full-text

Simultaneous Determination of Imatinib and N-Desmethyl Imatinib in Rat Plasma and Tissues Using LC-MS/MS

Current Pharmaceutical Analysis ◽

10.2174/1573412913666170821124952 ◽

2019 ◽

Vol 15 (2) ◽

pp. 121-129

Author(s):

Zhi Rao ◽

Bo-xia Li ◽

Yong-Wen Jin ◽

Wen-Kou ◽

Yan-rong Ma ◽

...

Keyword(s):

Bone Marrow ◽

Oral Administration ◽

Parent Drug ◽

Gradient Elution ◽

Biological Tissues ◽

Rat Plasma ◽

Running Water ◽

Liver And Kidney ◽

The Brain

Background: Imatinib (IM) is a chemotherapy medication metabolized by CYP3A4 to Ndesmethyl imatinib (NDI), which shows similar pharmacologic activity to the parent drug. Although methods for determination of IM and/or NDI have been developed extensively, only few observations have been addressed to simultaneously determine IM and NDI in biological tissues such as liver, kidney, heart, brain and bone marrow. Methods: A validated LC-MS/MS method was developed for the quantitative determination of imatinib (IM) and N-desmethyl imatinib (NDI) from rat plasma, bone marrow, brain, heart, liver and kidney. The plasma samples were prepared by protein precipitation, and then the separation of the analytes was achieved using an Agilent Zorbax Eclipse Plus C18 column (4.6 × 100 mm, 3.5 µm) with gradient elution running water (A) and methanol (B). Mass spectrometric detection was achieved by a triplequadrupole mass spectrometer equipped with an electrospray source interface in positive ionization mode. Results: This method was used to investigate the pharmacokinetics and the tissue distributions in rats following oral administration of 25 mg/kg of IM. The pharmacokinetic profiles suggested that IM and NDI are disappeared faster in rats than human, and the tissue distribution results showed that IM and NDI had good tissue penetration and distribution, except for the brain. This is the first report about the large penetrations of IM and NDI in rat bone marrow. Conclusion: The method demonstrated good sensitivity, accuracy, precision and recovery in assays of IM and NDI in rats. The described assay was successfully applied for the evaluation of pharmacokinetics and distribution in the brain, heart, liver, kidney and bone marrow of IM and NDI after a single oral administration of IM to rats.

Download Full-text