UHPLC-MS Simultaneous Determination and Pharmacokinetic Study of Three Aromatic Acids and One Monoterpene in Rat Plasma after Oral Administration of Shaofu Zhuyu Decoction

2013 ◽  
Vol 41 (03) ◽  
pp. 697-715 ◽  
Author(s):  
Shulan Su ◽  
Wenxia Cui ◽  
Jin-Ao Duan ◽  
Yongqing Hua ◽  
Jianming Guo ◽  
...  
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Study ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Rat Plasma ◽  
Negative Ion ◽  
Aromatic Acids ◽  
Active Components ◽  
Negative Ion Mode

We developed a sensitive and rapid method for determination of ferulic acid, caffeic acid, vanillic acid, and paeoniflorin in rat plasma based on ultra high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS). The separation of the four compounds was carried out on an AcQuity UHPLC™ BEH C18 column using a mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). Electrospray ionization in positive and negative ion mode and multiple reaction monitoring was used to identify and quantify active components. All calibration curves gave good linearity (r > 0.991) over the concentration range from 4.24–2875 ngmL-1 for all components. The precision of the in vivo study was evaluated by intraday and interday assays and the percentages of RSD were all within 10.6%. The recovery ranged from 60.2 to 77.9%. The method was successfully applied to pharmacokinetic study of all three aromatic acids and one monoterpene in rat plasma. Furthermore, we compared the pharmacokinetics profile of the four compounds in normal and primary dysmenorrhea rats' plasma following oral administration of Shaofu Zhuyu decoction (SFZYD) and its ethanol supernatant extract (SFE).

scholarly journals An LC-MS/MS Method for Simultaneous Determination of the Toxic and Active Components of Cortex Periplocae in Rat Plasma and Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Li ◽  
Yang Li ◽  
Jin Li ◽  
Rui Liu ◽  
Jia Hao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Simple Liquid ◽  
Active Components ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass

A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the toxic and other active components including isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract to rats. Plasma samples were prepared by protein precipitation with methanol. All compounds were separated on a C18 column with gradient elution using acetonitrile and formic acid aqueous solution (0.1%, v/v) as the mobile phase at a flow rate of 0.3 mL/min. The detection of all compounds was accomplished by multiple-reaction monitoring (MRM) in the positive electrospray ionization mode. The LC-MS/MS method exhibited good linearity for five analytes. The lower limit of quantification (LLOQ) was 0.48 ng/mL for scopoletin, periplogenin, and periplocymarin; 2.4 ng/mL for isovanillin and periplocin. The extraction recoveries of all compounds were more than 90% and the RSDs were below 10%. It was found that the absorption of scopoletin and periplocin was rapid in vivo after oral administration of cortex periplocae extract. Furthermore, periplocymarin possessed abundant plasma exposure. The results demonstrated that the validated method was efficiently applied for the pharmacokinetic studies of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract.

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.

Comprehensive and Rapid Identification of Astilbin Metabolites in Rats Based on Multiple Metabolite Templates Combined with UHPLC-Q-ExactiveMass Spectrometry

2021 ◽  
Vol 22 ◽  
Author(s):  
Shan Jiang ◽  
Haoran Li ◽  
Ailin Yang ◽  
Hongbing Zhang ◽  
Pingping Dong ◽  
...  
Keyword(s):  
Mass Spectrometer ◽  
Biological Effects ◽  
Rat Plasma ◽  
Rapid Identification ◽  
Negative Ion ◽  
Ring Cleavage ◽  
Rat Urine ◽  
Q Exactive ◽  
Negative Ion Mode

Background : Astilbin, a dihydroflavonoid compound widely found in plants, exhibits a variety of pharmacological activities and biological effects. However, little is known about the metabolism of this active compound in vivo, which is very helpful for elucidating the pharmacodynamic material basis and application of astilbin. Objective: To establish a rapid profiling and identification method for metabolites in rat urine, faeces and plasma using a UHPLC-Q-Exactive mass spectrometer in negative ion mode. Methods: In this study, a simple and rapid systematic strategy and 7 metabolite templates, which were established based on previous reports, were utilized to screen and identify astilbin metabolites. Results: As a result, a total of 72 metabolites were detected and characterized, among which 33 metabolites were found in rat urine, while 28 and 38 metabolites were characterized from rat plasma and faeces, respectively. These metabolites were presumed to be generated through ring cleavage, sulfation, dehydrogenation, methylation, hydroxylation, glucuronidation, dehydroxylation and their composite reactions. Conclusion: This study illustrated the capacity of the sensitive UHPLC-Q-Exactive mass spectrometer analytical system combined with the data-mining methods to rapidly elucidate the unknown metabolism. Moreover, the comprehensive metabolism study of astilbin provided an overall metabolic profile, which will be of great help in predicting the in vivo pharmacokinetic profiles and understanding the action mechanism of this active ingredient.

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

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.

scholarly journals Profiling and Pharmacokinetic Studies of Alkaloids in Rats After Oral Administration of Zanthoxylum nitidum Decoction by UPLC-Q-TOF-MS/MS and HPLC-MS/MS

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 585 ◽  
Author(s):  
Aihua Huang ◽  
Yuguang Chi ◽  
Jiawei Liu ◽  
Mincun Wang ◽  
Jialiang Qin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Oral Administration ◽  
High Performance ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Flight Mass Spectrometry ◽  
Zanthoxylum Nitidum

Zanthoxylum nitidum (Roxb.) DC (Rutaceae), called as “liangmianzhen” in China, is well known for its anti-inflammation and analgesic effect. Alkaloids are its main active constituents. However, little has been known about the absorption of main alkaloids in vivo. In this study, an ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was employed for identification of absorbed alkaloids in rats after oral administration of Z. nitidum decoction. By analyzing the fragmentation patterns, a total of nineteen alkaloids were exactly or tentatively identified in rat plasma after treatment, of which magnoflorine, α-allocryptopine, and skimmianine are dominant. Moreover, a high performance liquid chromatography coupled mass spectrometry method was developed for simultaneous quantification of magnoflorine, α-allocryptopine, and skimmianine, and successfully applied to pharmacokinetic study in rats after oral administration of Z. nitidum decoction. The research would contribute to comprehensive understanding of the material basis and function mechanism of Z. nitidum decoction.

Simultaneous Determination of Saponins and Lignans in Rat Plasma by UPLC-MS/MS and its application to a pharmacokinetic study of Shenqi Jiangtang Granule

2021 ◽  
Vol 22 ◽  
Author(s):  
Hui Zhang ◽  
Ruoyu Chen ◽  
Cong Xu ◽  
Ya Zhang ◽  
Qinghua Tian ◽  
...  
Keyword(s):  
Oral Administration ◽  
Simultaneous Determination ◽  
High Performance ◽  
Negative Ion ◽  
Schisandrin B ◽  
Limit Of Quantification ◽  
Ginsenoside Re ◽  
Ginsenoside Rd

Background: Shenqi Jiangtang Granule (SJG), a classical prescription of traditional Chinese medicine, is widely used to treat diabetes and its complications. Despite the clinical efficacy of SJG is effective, pharmacokinetic behavior of various substance in plasma of SJG are unknown. Objective: The aim of this study was to investigate the plasma pharmacokinetics during absorption of SJG after oral administration in rats. Methods: A rapid and accurate ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of eight analytes in SJG, including gomisin D, schisandrin A, schisandrin B, schizandrol A, schizandrol B, ginsenoside Rd, ginsenoside Re and notoginsenoside Ft1. The analysis was carried out on a BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with gradient elution at a flow rate of 0.2 mL/min in a mobile phase consisting of 0.1% formic acid water and acetonitrile. In addition, lignans and saponins were detected in positive ion mode and negative ion mode, respectively. Results: Eight analytes in SJG, including gomisin D, schisandrin A, schisandrin B, schizandrol A, schizandrol B, ginsenoside Rd, ginsenoside Re and notoginsenoside Ft1, showed good linearity (R2 in the range of 0.9955~0.9999). The lower limit of quantification (LLOQ) was 5, 0.8, 0.8, 8, 0.8, 5, 0.6 and 10 ng/mL. Accuracy and precision of all analytes were at ±15%. Matrix effect and average extraction recovery were > 85%. All analytes performed well under four storage conditions. Conclusions: The results showed that in vivo absorption and exposure of gomisin D and ginsenoside Rd were better than other analytes, while schizandrol B and notoginsenoside Ft1 were poorly absorbed. This approach could be applied to study the pharmacokinetic characteristics of various analytes in plasma after oral administration of SJG in rats.

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

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2980 ◽  
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.

scholarly journals Simultaneous Determination of Seven Active Components in Rat Plasma by UHPLC-MS/MS and Application to a Quantitative Study after Oral Administration of Huang-Lian Jie-Du Decoction in High Fat-Induced Atherosclerosis Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Li Jiang ◽  
Yanling Xiong ◽  
Lanbin Yu ◽  
Yu Chen ◽  
Qiyun Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Simultaneous Determination ◽  
Quantitative Study ◽  
High Performance ◽  
Rat Plasma ◽  
Dependent Manner ◽  
High Fat ◽  
Active Components ◽  
Validation Parameters

Huang-Lian Jie-Du decoction (HLJDD) has been used to treat cardiovascular and cerebrovascular disease for many years in China. Currently, the determination of effect components in HLJDD is focusing either on the formula or on the extract, while quantification of that in biological samples is scarce, especially simultaneous determination of multicomponent. In this paper, a rapid, specific, and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method was developed and fully validated for the simultaneous determination of seven main active constituents, i.e., baicalin, baicalein, wogonoside, wogonin, berberine, palmatine, jatrorrhizine in rat plasma. The method was also successfully applied to a quantitative study after oral administration of HLJDD at different doses of 1.5, 3, and 6 g/kg body weight to high fat-induced atherosclerosis rats. The analytes were detected by ESI source and multiple reactions monitoring (MRM) using positive scanning mode. The blood was collected from the abdominal aorta of rats at predetermined time and preprepared with icariin and tetrahydropalmatine as internal standards (IS). Sample preparation was achieved by protein precipitation (PPT). The validation parameters (linearity, sensitivity, intra-/interday precision and accuracy, extraction recovery, and matrix effect) were within acceptable ranges, and biological extracts were stable during the entire storing and preparing process. And the result of determination of HLJDD-containing plasma, baicalin, baicalein, wogonoside, and wogonin could be highly detected in a dose-dependent manner while berberine, jatrorrhizine, and palmatine were determined in a very low level and in a dose-independent mode. Thus, the established method was sensitive enough and successfully applied to the determination of seven effective components in plasma taken from 24 high fat-induced atherosclerosis rats after oral administration of three dosages of HLJDD.

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