scholarly journals Studies of the pharmacokinetics of morroniside and loganin in rat after oral administration of raw and wine-processed Corni fructus by UPLC-QqQ-MS/MS

2022 ◽  
Vol 20 (2) ◽  
pp. 411-418
Author(s):  
Wei Wang ◽  
Xuechun Wang ◽  
Qiang Zhang ◽  
Ru Jia ◽  
Chunjie Du ◽  
...  

Purpose: To study the pharmacokinetics of morroniside (MR) and loganin (LG) in rats after oral administration of raw and wine-processed Corni fructus by UPLC-QqQ-MS/MS. Methods: Arctiin (AT) was used as internal standard, and the plasma or tissue samples were extracted twice using ethyl acetate. Electrospray ionization (ESI) negative ion mode was used, and the multiple reaction monitoring mode (MRM) was set in acquisition mode. The extraction and detection method is supported by selectivity, sensitivity, precision, accuracy, stability, extraction, recovery and matrix effect. The non-atrioventricular model of das2.0 software was used to calculate the pharmacokinetic parameters. Results: The absorption rate of MR (PTmax=0.092) and LG (PTmax=0.092) in Corni Fructus after wine-processing was faster in rats. The mean residence time was longer, and distribution of MR (PMRT0~t = 0.294) and LG (PMRT0~t = 0.000) in wine-processed Corni Fructus group increased in liver and kidneys. Conclusion: The proposed method has been successfully validated and is suitable for studying the pharmacokinetics of the two analytes in rats.

Author(s):  
Revathi Naga Lakshmi Ponnuri ◽  
Prahlad Pragallapati ◽  
Ravindra N ◽  
Venkata Basaveswara Rao Mandava

  Objective: The main objective of the work was to develop a straightforward, fast and selective liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for determination of pioglitazone (PG), keto pioglitazone (KPG), and hydroxy pioglitazone (HPG) in human plasma and to validate as per recent guidelines.Methods: Analyte and the internal standard (IS) were extracted from plasma through liquid-liquid extraction and chromatographed on a Xterra RP18, 100×4.6, 5 μ column using methanol: acetonitrile mixture and 10 mM Ammonium formate buffer (70:30, v/v) as the mobile phase at a flow rate of 0.7 mL/min. The API-3200 Q Trap LC-MS/MS instrument in multiple reaction monitoring mode was used for detection. Diphenhydramine was utilized as IS.Results: The linearity was established in the concentration range of 20.15-1007.58 ng/mL for PG, 20.35-1017.58 ng/mL for KPG, and 19.68-491.22 ng/mL for HPG in human plasma. All the validation parameters were well within the acceptance limits.Conclusion: A new simple LC-MS/MS method was developed for the determination of PG, KPG, and HPG in human plasma. This method can be easily applied for the estimation of pharmacokinetic parameters of PG, KPG, and HPG.


2020 ◽  
Vol 15 (6) ◽  
pp. 1934578X2092944
Author(s):  
Na Li ◽  
Ting Lv ◽  
Jie Pan ◽  
Chunhua Liu ◽  
Jia Sun ◽  
...  

A simple, rapid, and selective ultra-performance liquid chromatography-mass spectrometry (MS)/MS method was established to investigate tissue distribution of 6 polyphenolic compounds of Polygonum orientale L. extract in normal and myocardial ischemia (MI) model rat tissues, including isoorientin, orientin, vitexin, quercitrin, astragalin, and protocatechuic acid. An Agilent Eclipse Plus C18 column was used. The mobile phase consisted of acetonitrile and water, both with 0.1% formic acid. Quantification was performed in negative ion multiple reaction monitoring mode. All the analysts had good linearity with r ≥ 0.9912. Accuracy ranged from 12.49% to −13.98% for the 6 compounds; within-day variation (precision) was ≤9.98% and interday precision was ≤11.88%. Extraction recovery of the analysts ranged from 80.55% to 99.92%; the matrix was 81.00%–98.73%. The analyst preparations were stable throughout. The 6 compounds were rapidly distributed in various tissues after oral administration, without accumulation over 12 hours. Compared with normal rats, distributions of 6 compounds in the heart, liver, spleen, lung, kidney, brain, stomach, and intestine in MI model rats were different from those in the normal group. The study provides an insight for further research of P. orientale L.


2020 ◽  
Vol 19 (3) ◽  
pp. 651-659
Author(s):  
Xin Jia ◽  
Yinfei Du ◽  
Jia Xu ◽  
Yu Dong

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


2012 ◽  
Vol 5 (1) ◽  
pp. 31-36 ◽  
Author(s):  
L. Xiang ◽  
Y. Gao ◽  
D. Liu ◽  
M. Yang

An HPLC-tandem mass spectrometry method was developed for the determination of patulin (PAT) in dried medicinal hawthorn fruit, a well-known traditional medicine in China. Liquid-liquid extraction was applied in the sample preparation. Multiple reaction monitoring was performed at m/z 153/109 for PAT and m/z 317/273 for internal standard zearalenone in the negative ion mode with electrospray ionisation source. Good linearity was achieved when spiked PAT concentrations were in the range of 10-500 μg/kg, with coefficient being 0.9993. The limit of quantitation was 10 μg/kg. The extraction recoveries for the spiked PAT at concentrations of 20, 100 and 400 μg/kg were 64.5%, 64.6% and 63.9%, respectively, with relative standard deviations of 1.25%, 2.82% and 2.61%. The intra-day and inter-day precision were in the range of 2.2-9.6% and 5.9-6.4%. This rapid, sensitive and reliable method was applied in 25 batches of medicinal hawthorn fruit, in which PAT was detected in 8 batches, including those that were baked or charred.


2020 ◽  
Vol 16 ◽  
Author(s):  
Yihe Huang ◽  
Yanhui Zhao ◽  
Yumeng Zhang ◽  
Lin Sun ◽  
Chunjie Zhao ◽  
...  

Background: Danyikangtai powder, a traditional Chinese medicine (TCM) formula, shows promise to become a novel drug candidate for the simultaneous treatment of chronic cholecystitis and chronic pancreatitis. However, the pharmacokinetic behavior of Danyikangtai powder remains unclear. Objective: We investigated the comparative pharmacokinetics of four flavonoids in rats after oral administration of Danyikangtai powder and three compatibilites. Materials and methods: The comparative pharmacokinetics was studied by ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS). Chromatographic separation was performed on an Universil XB-C18 column with a gradient mobile phase containing 0.1% (v/v) aqueous formic acid and acetonitrile. All analytes and internal standard were quantitated in the multiple reaction monitoring mode with a positive electrospray ionization interface. Results and discussion: Danyikangtai powder and Scutellariae radix have similar pharmacokinetic behaviors in rats after oral administration. However, the elimination of four flavonoids in rats after oral administration of Danyikangtai powder was accelerated, which was possibly related to the reduction of the potential hepatotoxicity of Scutellariae radix. The varying degrees of change in pharmacokinetic parameters after oral administration of different herb combinations suggested that herb–herb interactions occurred in vivo. Conclusions: This study will be helpful to reveal the safety, rational and mechanism of Danyikangtai powder formula compatibility, thereby providing pre-clinical research data for its new drug development and guidance for its rational clinical application.


2020 ◽  
Vol 58 (10) ◽  
pp. 922-928
Author(s):  
Jing Zhang ◽  
Quan Wen ◽  
Meng-ying Zhou ◽  
Chen-cong Zhong ◽  
Yulin Feng ◽  
...  

Abstract Chimonanthi Radix (CR) is widely used in the treatment of influenza in China. Extensive studies revealed that the major bioactive constituents of CR were coumarins. However, pharmacokinetic study of coumarins in CR has not been fully studied. The purpose of this study was to establish a convenient and effective high-performance liquid chromatography–tandem mass spectrometry method that was used to simultaneously determine scopoletin, scopolin and isofraxidin in rat plasma after oral administration of CR extract using xanthotoxin as the internal standard. The chromatographic separation was carried out on a COSMOCORE C18 column (100 × 2 mm, 2.6 μm), using gradient elution with the mobile phase consisting of 0.1% formic acid (A) and acetonitrile (B). Three coumarins and IS were quantified by positive ion electrospray ionization in multiple reaction monitoring mode. The method was fully validated in terms of specificity, accuracy, precision (intra- and inter-day), matrix effect, recovery as well as the stability of the analytes under various conditions. The results could provide further research foundation for anti-influenza mechanism of three coumarins in CR.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Feili Wei ◽  
Li Guo ◽  
Yongsong Xu ◽  
Dexi Chen ◽  
Muxin Gong

Fructus polygoni orientalis (FPO) is widely used in clinical practice in China, especially in treatment of liver diseases including viral hepatitis, liver fibrosis, and liver cirrhosis. However, its pharmacokinetic (PK) alterations in liver fibrotic rats have rarely been reported. To study whether taxifolin, one of the main flavonoids in FPO can be absorbed into blood after oral administration of FPO extract and to compare the differences in pharmacokinetic parameters of taxifolin to normal and liver fibrotic rats induced by porcine serum (PS), a UPLC-MS/MS method was developed and validated for determination of taxifolin in rat plasma using puerarin as the internal standard (IS). All validation parameters met the acceptance criteria according to regulatory guidelines. The results indicated that after treatment of rats with PS alone for 12 weeks, the liver fibrotic model group was built successfully. The taxifolin can be absorbed into the blood after oral administration of the FPO extract. The Cmax of taxifolin was 1940 ± 502.2 ng/mL and 2648 ± 208.5 ng/mL (p<0.05), the AUC0∼t of taxifolin was 4949.7 ± 764.89 h·ng/mL and 6679.9 ± 734.26 h·ng/mL (p<0.05), the AUC0∼∞ of taxifolin was 5049.4 ± 760.7 and 7095.2 ± 962.3 h·ng/mL (p<0.05), and the mean residence time (MRT) of taxifolin was 2.46 ± 0.412 h and 3.17 ± 0.039 h (p<0.05) in the normal and fibrotic model groups, respectively. These results confirmed that the pharmacokinetic parameters of taxifolin are altered in liver fibrosis, manifested as Cmax, AUC0∼t, AUC0∼∞, and the mean residence time (MRT). It suggested that it is essential to consider the characteristics of pharmacokinetics after oral administration of FPO in liver disease patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yuqi Fan ◽  
Lulu Zhao ◽  
Xuhua Huang ◽  
Jiayuan Shen ◽  
Wei Wang ◽  
...  

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.


Author(s):  
Mehmet Emrah Yaman ◽  
Alptug Atila ◽  
Tugrul Cagri Akman ◽  
Mevlut Albayrak ◽  
Yucel Kadioglu ◽  
...  

Abstract For the quantification of flurbiprofen in rat plasma, a simple UPLC-MS/MS method with high sensitivity and short retention time for flurbiprofen was developed and validated using specific parameters. Etodolac was used as internal standard. The transitions (precursor to the product) of flurbiprofen and internal standard were obtained using the electrospray ionization in the negative ion multiple reaction monitoring mode, 243.2 → 199.2, 286.2 → 212.1, respectively. For chromatographic separation, C18 column was used for the stationary phase and gradient elution was used for the mobile phase. This mobile phase consisted of a methanol (A) and a 5 mM ammonium formate solution (B), which varied at a flow rate of 0.4 mL/min. For flurbiprofen, LLOQ was determined as 5 ng/mL. Quantification of flurbiprofen in the rat plasma with a linear calibration curve of 5–5000 ng/mL (r &gt; 0.9991 for plasma) is possible with a retention time of 1.89 min. The total analysis time of the method was 3 min. The proposed method was validated. The intraday and inter-day precision (RSD%) and accuracy (RE%) were within 10% in all cases for flurbiprofen. The stability of flurbiprofen was evaluated under conditions such as short-term, long-term, autosampler and freeze/thaw. After method validation, flurbiprofen was succesfully quantified in real rat plasma samples.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3234 ◽  
Author(s):  
Shizhao Xu ◽  
Xiaojie Qi ◽  
Yuqiang Liu ◽  
Yuhan Liu ◽  
Xin Lv ◽  
...  

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.


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