scholarly journals UPLC-MS/MS Method for the Simultaneous Quantification of Eight Compounds in Rat Plasma and Its Application to a Pharmacokinetic Study after Oral Administration of Veratrum (Veratrum nigrum L.) Extract

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yuqi Fan ◽  
Lulu Zhao ◽  
Xuhua Huang ◽  
Jiayuan Shen ◽  
Wei Wang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Internal Standard ◽  
Rat Plasma ◽  
Negative Ion ◽  
Pharmacokinetic Parameters ◽  
Relative Standard ◽  
Antifungal Effects ◽  
The Matrix ◽  
The Stability

Veratrum nigrum L. is a well-known traditional Chinese medicine with a lot of pharmacological activities including antihypertensive, anticancer, and antifungal effects. In the current experiment, a rapid and sensitive UPLC-MS/MS method that takes only 7 min run time has been established and validated for simultaneous determination of eight bioactive compounds including cyclopamine, jervine, veratramine, polydatin, quercetin, apigenin, resveratrol, and veratrosine in rat plasma. The chromatographic separation of analytes and internal standard was performed on a Phenyl-Hexyl column ( 2.1 × 100   mm , 1.7 μm) with the mobile phase consisting of water (0.1% formic acid) and acetonitrile at a flow rate of 0.3 mL/min. An electrospray ionization (ESI) source was used to detect the samples in both positive and negative ion modes. The intra- and interday precisions of the compounds were less than 9.5% and the accuracy ranged from -10.8% to 10.4%. The extraction recoveries of the compounds were in the range of 85.1 ± 1.5 % to 102.6 ± 8.0 % , and the matrix effect ranged from 91.2 ± 4.5 % to 113.8 ± 1.5 % . According to the results of the stability test, the eight compounds have good stability under various conditions and the relative standard deviation (RSD) less than 13.2%. The pharmacokinetic parameters of the eight compounds in rat plasma after oral administration of Veratrum nigrum L. extract were successfully determined by the established UPLC-MS/MS method.

scholarly journals Comparative pharmacokinetic study of five flavonoids in normal rats and rats with gastric ulcer following oral administration of Mongolian medicine, Shudage - 4 by UPLC – ESI – MS/MS

2020 ◽  
Vol 19 (3) ◽  
pp. 651-659
Author(s):  
Xin Jia ◽  
Yinfei Du ◽  
Jia Xu ◽  
Yu Dong
Keyword(s):  
Gastric Ulcer ◽  
Oral Administration ◽  
Internal Standard ◽  
Rat Plasma ◽  
Negative Ion ◽  
Selected Reaction Monitoring ◽  
Pharmacokinetic Parameters ◽  
Ionization Mass ◽  
Plasma Samples ◽  
Esi Ms

Purpose: To develop a simple, rapid and sensitive ultra-performance liquid chromatography - electrospray ionization-mass spectrometry (UPLC–ESI–MS/MS) method was developed and fully validated for the simultaneous determination of galangin, kaempferide, galangin-3-methylether, kaempferol and quercetin in rat plasma after oral administration of Mongolian Medicine, Shudage-4 extracts. Methods: The galangin, kaempferide, galangin-3-methylether, kaempferol and quercetin were separated on a C18 column using 0.1 % formic acid at a flow rate of 0.4 mL / min and detected by a mass spectrometer in negative-ion mode with selected reaction monitoring (SRM) mode. Plasma samples were processed with a simple deproteinization technique using ethyl acetate and acetonitrile. Following the protein precipitation, the plasma samples were evaporated under gentle stream of nitrogen and analyzed by above method. Naringin was used as an internal standard (IS). Method validation was performed according to the Chinese Food and Drug Administration guidelines. Results: A good linearity (r2 ≥ 0.9990) was showed by the UPLC – ESI – MS / MS method, the low limits of quantification for galangin, kaempferide, galangin-3-methylether, kaempferol and quercetin were 229.8, 78.8, 32.0, 123.7 and 137.8 ng / mL, respectively. The results of inter-day and intra-day precisions met the experimental requirement (< 7.8 %). The matrix effect and recovery efficiency of the five analytes were more than 72.9 and 88.7 % respectively. The stability of the analytes were satisfactory. The UPLC – ESI – MS / MS method has been used for the five analytes’ pharmacokinetics study successfully after gastrointestinal route of the Mongolian Medicine Shudage-4. The pharmacokinetic parameters showed significant differences (P < 0.05) between the normal and gastric ulcer groups. The metabolism and transport of the five analytes in gastric ulcer rates were faster than in normal rats after administration of Shudage - 4 extract. Double-peak phenomenon appeared in galangin, galangin – 3 - methylether and quercetin. Conclusion: The results suggest that the metabolism and transport of Mongolian Medicine Shudage-4 in gastric ulcer rats is faster than in normal rats and may be enriched and acted on at the lesion site. Keywords: UPLC – ESI – MS / MS; Mongolian medicine; Shudage - 4; pharmacokinetics; gastric ulcer

Quantitative Determination of Quercitrin Levels in Rat Plasma Using UHPLC-MS/MS and its Application in a Pharmacokinetic Study after the Oral Administration of Polygoni Cuspidati Folium Capsules

2021 ◽  
Vol 22 ◽  
Author(s):  
Shi-tang Ma ◽  
Xin-yuan Zhang ◽  
Ning Zhang ◽  
Xiao-lin Bi ◽  
Cheng-Tao Feng
Keyword(s):  
Mass Spectrometry ◽  
Oral Administration ◽  
Quantitative Determination ◽  
Biological Activities ◽  
Rat Plasma ◽  
Negative Ion ◽  
Pharmacokinetic Parameters ◽  
Peripheral Tissues ◽  
Wide Range

Background: Quercitrin is widely found in herbal medicines, and it is particularly important in the design of new therapeutic agents. Because of its wide range of biological activities, methods for detecting quercitrin and its pharmacokinetics in biological samples must be investigated. Objective: To develop and validate a sensitive and reliable ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the quantitative determination of quercitrin levels in rat plasma and test its application in a pharmacokinetic investigation after the oral administration of Polygoni cuspidati folium capsules (HC). Methods: First, a rapid analytical method implementing UHPLC-MS/MS for the quantification of quercitrin levels in rat plasma was developed and validated. The analyte and internal standard (IS) tinidazole were extracted from rat plasma via protein precipitation with 800 μL of methanol and 50 μL of 1% formic acid solution. Chromatographic separation was performed using an Agilent ZORBAX C18 column within 4 min. Mass spectrometry was performed for quantification using a triple-quadrupole mass spectrometer employing electrospray ionization in the negative ion mode. The MRM transitions for quercitrin and IS were m/z 447.2→229.9 and m/z 246.0→125.8, respectively. The UHPLC-MS/MS method for the quantitative determination of quercitrin levels in rat plasma was then applied to investigate its pharmacokinetics after the oral administration of HC in rats. Results: The developed UHPLC-MS/MS method for detecting quercitrin in rat plasma was linear over the range of 0.1–160 ng/mL. The linear regression equation was Y = (0.7373 ± 0.0023)X − (0.0087 ± 0.0021) (r2 = 0.9978). The intra- and interday precision values were within 7.8%, and the recoveries of quercitrin and IS exceeding 67.3%. The UHPLC-MS/MS method was successfully applied to characterize the pharmacokinetic profile of quercitrin in eight rats after the oral administration of HC. The experimentally obtained values were fit to a one-compartment, first-order pharmacokinetic model, and they appeared to fit the concentration-time curve. Conclusion: Quercitrin was proven to be stable during sample storage, preparation, and analytical procedures. The pharmacokinetic parameters suggested that quercitrin may be present in the peripheral tissues of rats.

scholarly journals UPLC-MS/MS of Atractylenolide I, Atractylenolide II, Atractylenolide III, and Atractyloside A in Rat Plasma after Oral Administration of Raw and Wheat Bran-Processed Atractylodis Rhizoma

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3234 ◽  
Author(s):  
Shizhao Xu ◽  
Xiaojie Qi ◽  
Yuqiang Liu ◽  
Yuhan Liu ◽  
Xin Lv ◽  
...  
Keyword(s):  
Oral Administration ◽  
Wheat Bran ◽  
Multiple Reaction Monitoring ◽  
Area Under The Curve ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Weighting Method ◽  
Relative Standard

Atractylodis Rhizoma is the dried rhizome of Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz and is often processed by stir-frying with wheat bran to reduce its dryness and increase its spleen tonifying activity. However, the mechanism by which the processing has this effect remains unknown. To explain the mechanism based on the pharmacokinetics of the active compounds, a rapid, sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was developed to analyze atractylenolides I, II, and III, and atractyloside A simultaneously in rat plasma after oral administration of raw and processed Atractylodis Rhizoma. Acetaminophen was used as the internal standard and the plasma samples were pretreated with methanol. Positive ionization mode coupled with multiple reaction monitoring mode was used to analyze the four compounds. The method validation revealed that all the calibration curves displayed good linear regression over the concentration ranges of 3.2–350, 4–500, 4–500, and 3.44–430 ng/mL for atractylenolides I, II, and III, and atractyloside A, respectively. The relative standard deviations of the intra- and inter-day precisions of the four compounds were less than 6% with accuracies (relative error) below 2.38%, and the extraction recoveries were more than 71.90 ± 4.97%. The main pharmacokinetic parameters of the four compounds were estimated with Drug and Statistics 3.0 and the integral pharmacokinetics were determined based on an area under the curve weighting method. The results showed that the integral maximum plasma concentration and area under the curve increased after oral administration of processed Atractylodis Rhizoma.

scholarly journals Pharmacokinetic Study of Thirteen Ingredients after the Oral Administration of Flos Chrysanthemi Extract in Rats by UPLC-MS/MS

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Qi Jia ◽  
Xuhua Huang ◽  
Guangzhe Yao ◽  
Wenjuan Ma ◽  
Jiayuan Shen ◽  
...  
Keyword(s):  
Oral Administration ◽  
Bioactive Compounds ◽  
Pharmacokinetic Study ◽  
Rat Plasma ◽  
Negative Ion ◽  
Pharmacokinetic Parameters ◽  
Phase System ◽  
Limit Of Quantification ◽  
Relative Standard ◽  
Acquity Uplc

A rapid and reliable UPLC-MS/MS method was developed and validated for the simultaneous quantification of thirteen bioactive compounds (luteolin, cynaroside, luteolin 7-O-glucuronide, isochlorogenic acid C, chlorogenic acid, cryptochlorogenic acid, apigenin, apigenin 7-glucoside, acacetin, hyperoside, isoquercitrin, tilianin, and hesperidin) in rat plasma. The compounds were separated on an ACQUITY UPLC BEH C18 column (2.1×100 mm, 1.7 μm) with a gradient mobile phase system of acetonitrile and 0.1% (v/v) formic acid aqueous solution at a flow rate of 0.3 mL/min. All compounds were quantitated using Agilent Jet Stream electrospray ionization (AJS ESI) in a negative ion mode. The lower limit of quantification (LLOQ) for all compounds was below 5 ng/mL. The intra- and interday accuracy ranged from -13.0% to 14.0%, and precisions were less than 12.2%. The extraction recoveries of the compounds were in the range of 56.9% to 95.0%, and the matrix effect ranged between 71.6% and 109.3%. Stability studies proved that the thirteen compounds were stable under tested conditions, with a relative standard deviation (RSD) of less than 11.4%. This developed method was successfully applied to the pharmacokinetic study of the 13 bioactive compounds after oral administration of Flos Chrysanthemi extract in rat by UPLC-MS/MS. Pharmacokinetic parameters of 8 out of the 13 compounds investigated are presented in this paper.

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

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
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.

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

Bioanalysis ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 11-22 ◽  
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.

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

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
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.

scholarly journals Determination of Lekethromycin, a Novel Macrolide Lactone, in Rat Plasma by UPLC-MS/MS and Its Application to a Pharmacokinetic Study

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4676
Author(s):  
Hongzhi Xiao ◽  
Pan Sun ◽  
Jicheng Qiu ◽  
Jianzhong Wang ◽  
Lei Yan ◽  
...  
Keyword(s):  
Electrospray Ionization ◽  
Matrix Effects ◽  
High Resolution Mass Spectrometry ◽  
Internal Standard ◽  
Gradient Elution ◽  
Storage Conditions ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Limit Of Quantification ◽  
Relative Standard

Lekethromycin, a new macrolide lactone, exhibits significant antibacterial activity. In this study, a reliable analytical ultrahigh-performance liquid chromatography electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UPLC-ESI-Orbitrap-MS) method was established and validated for the detection of lekethromycin in rat plasma. After a simple acetonitrile (ACN)-mediated plasma protein precipitation, chromatographic separation was performed on a Phenomenex Luna Omega PS C18 column (30 × 2.1 mm i.d. particle size = 3 μm) conducted in a gradient elution procedure using 0.5% formic acid (FA) in ACN and 0.5% FA in water as the mobile phase pumped at a flow rate of 0.3 mL/min. Detection was carried out under positive electrospray ionization (ESI+) conditions in parallel reaction monitoring (PRM) mode with observation of m/z 804.5580 > 577.4056 for lekethromycin and 777.5471 > 619.4522 for gamithromycin (internal standard, IS). The linear range was 5–1000 ng/mL (r2 > 0.99), and the lower limit of quantification (LLOQ) was 5 ng/mL. The intra- and inter-day precision (expressed as relative standard deviation, RSD) values were ≤7.3% and ≤6.3%, respectively, and the accuracy was ≥90% ± 5.3%. The mean extraction recovery RSD valWeue was <5.1%. Matrix effects and dilution integrity RSD values were <5.6% and <3.2%, respectively. Lekethromycin was deemed stable under certain storage conditions. This fully validated method was effectively applied to study the pharmacokinetics of lekethromycin after a single intravenous administration of 5 mg/kg in rats. The main pharmacokinetic parameters were T1/2λz, CL_obs and VZ_obs were 32.33 ± 14.63 h, 0.58 ± 0.17 L/h/kg and 25.56 ± 7.93 L/kg, respectively.

Simultaneous Determination of Kirenol, Rosmarinic Acid and Caffeic Acid in Rat Plasma and Pharmacokinetic Study After Oral Administration of the Extract of Manxingshizhen Preparation by UPLC-MS/MS

2018 ◽  
Vol 15 (1) ◽  
pp. 74-81 ◽  
Author(s):  
Shuo Sun ◽  
Xue Zhang ◽  
Linda Luo ◽  
Ping Wang ◽  
Mengxuan Bai ◽  
...  
Keyword(s):  
Oral Administration ◽  
Electrospray Ionization ◽  
Simultaneous Determination ◽  
Caffeic Acid ◽  
Pharmacokinetic Study ◽  
Rosmarinic Acid ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Tandem Mass Spectrometric

Introduction: A rapid, sensitive and convenient ultra-performance liquid chromatography with tandem mass spectrometric detection (UPLC-MS/MS) method has been validated and applied to the simultaneous determination of kirenol, rosmarinic acid and caffeic acid after oral administration of the extract of Manxingshizhen preparation in rat plasma. Materials and Methods: Puerarin was selected as the internal standard (IS). The plasma sample preparation was pretreated by liquid-liquid extraction of the mixture with ethyl acetate. All analytes were simultaneously detected in multiple reaction monitoring (MRM) mode via both the positive electrospray ionization (ESI+) and negative electrospray ionization (ESI). In the experiment, all calibration curves revealed good linearity (r > 0.999). The LLOQ were between 0.80-2.00 ng/mL, respectively. Besides, the intra-day and inter-day precision ranged from 6.4 to 13.8%, respectively. Moreover, the accuracy was within - 11.4% and 12.8% for all the QC levels of all analytes. The extraction recoveries of the analytes and IS in plasma at three concentration levels ranged from 88.5 to 103.2%, moreover, the matrix effects of all the analytes and the IS were found to be satisfied with the acceptable range of 89.8%-101.7%. Meanwhile, the RSD values of stability met the requirement of not more than 15%. Furthermore, the pharmacokinetic parameters of three compounds were analyzed using concentrationtime profiles. Conclusion and Results: Plasma concentrations of the three compounds were determined up to 24 h after oral administration, and their pharmacokinetic parameters were in agreement with previous studies. The validated method was successfully applied in a pharmacokinetic study in rat plasma after oral administration of Manxingshizhen preparation.

Determination of Acotiamide in human plasma by LC-MS/MS and its application to a pharmacokinetic study

2020 ◽  
Vol 17 ◽  
Author(s):  
Qian Sun ◽  
Qiao-gen Zou ◽  
Yun-yan Xia ◽  
Cheng-qun Han
Keyword(s):  
Human Plasma ◽  
Pharmacokinetic Study ◽  
Ammonium Acetate ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Tandem Mass Spectrometric

Background: A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method had been developed for the quantification of acotiamide in rat plasma and been applied to pharmacokinetic studies. However, there was no LC-MS/MS method been developed for the determination of acotiamide in human plasma and its pharmacokinetic study. Objective: A simple and fast LC-MS/MS method was established and validated for the quantification of acotiamide in human Received: plasma and was applied to a pharmacokinetic study. Methods: Sample preparation was accomplished Revised: Accepted: through protein precipitation, and chromatographic separation was achieved on a Welch, Ultimate XB-C18 column (2.1×50 mm, 3 μm) with a security guard cartridge C18 using a binary gradient with DOI: mobile phase A (Methanol) and B (the solution of 10 mM Ammonium acetate with 0.1% Formic acid) at a flow rate of 400 Results: The retention time of acotiamide and its internal standard, acotiamide-d6 was 1.78 min and 1.79 min, respectively. The total run time was 4.0 min. The method was developed and validated over the concentration range of 0.500-100 ng/mL for acotiamide, with correlation coefficient greater than 0.9987. The extraction recovery was more than 108.43% and the matrix effect was not significant. The inter- and intra-day precisions were below 5.80% and accuracies ranged from 92.7 to 103.0%. Acotiamide was demonstrated to be stable in human plasma under the tested conditions. Conclusion: The validated LC-MS/MS method was successfully applied to study the pharmacokinetic profiles of acotiamide in human plasma after oral administration and has achieved satisfactory results.

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