scholarly journals Simultaneous Quantification of Pioglitazone and Omarigliptin in Rat Plasma by UHPLC-MS/MS and Its Application to Pharmacokinetic Study after Coadministration of the Two Drugs

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Lin Wang ◽  
Jiaxi Wang ◽  
Chao Lin ◽  
Furong Wang ◽  
Xiangping Li ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Meta Analysis ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Ion Source ◽  
Pharmacokinetic Parameters ◽  
Column Temperature ◽  
Linear Relationships ◽  
Long Acting

Combination therapy is a common approach for clinical treatment of type 2 diabetes mellitus, especially for patients with poor monotherapy. Meta-analysis suggested that omarigliptin, a long-acting DPP-4 inhibitor, combined with pioglitazone might improve the side effects of pioglitazone. However, little is known about the pharmacokinetic properties after a coadministration. In this study, a rapid and reliable method for the simultaneous determination of the pioglitazone and omarigliptin in rat plasma by UHPLC-MS/MS was established and validated for the first time. An exsil mono C18 column (2.0 × 50 mm, 3 μm) was used to separate the analytes and the column temperature was kept at 30°C. Sitagliptin was selected as the internal standard. 0.02% formic acid aqueous solution (A) and methanol-acetonitrile (B) were used as mobile phases with gradient elution at a flow rate of 0.3 mL/min. The elution procedure was as follows: 20%B (0–0.1 min), 80%B (0.1–0.3 min), 80%B (0.3–2.0 min), and 20%B (2.1–3.0 min). A multiple reaction monitor (MRM) was used under positive ionization mode with electrospray ion source to detect pioglitazone (357.1 ⟶ 134.1), omarigliptin (399.2 ⟶ 153.0), and sitagliptin (408.2 ⟶ 235.0). The linear ranges of pioglitazone and omarigliptin were 5–2000 ng/mL and 10–4000 ng/mL, respectively. Good linear relationships were exhibited in the corresponding linear ranges (r ≥ 0.9944). The bioanalytical method was validated, and the selectivity, linearity, sensitivity, accuracy, precision, stability, recovery, and matrix effect were acceptable. The validated method was then successfully applied to pharmacokinetic study of pioglitazone combined with omarigliptin in rats. Results suggested that the combination of the two drugs had little effect on the pharmacokinetic parameters of each other in rats.

scholarly journals Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method

2021 ◽  
Vol 71 (3) ◽  
pp. 415-428
Author(s):  
Sai-Jie Zuo ◽  
Xiao-Liang Cheng ◽  
Dong-Zheng Liu ◽  
Wei-Yi Feng ◽  
Yong-Xiao Cao ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Growth Factor Receptor ◽  
Internal Standard ◽  
Gradient Elution ◽  
Storage Conditions ◽  
Rat Plasma ◽  
Selected Reaction Monitoring ◽  
Pharmacokinetic Parameters ◽  
Egfr Inhibitor ◽  
Reliable Quantification

Abstract1-(4-(Pyrrolidin-1-yl-methyl)phenyl)-3-(4-((3-(trifluoromethyl) phenyl)amino)quinazolin-6-yl)urea (ZCJ14), a novel epidermal growth factor receptor (EGFR) inhibitor, with diarylurea moiety, displays anticancer effect. In the present study, an LCMS/MS method was established to determine the concentration of ZCJ14 in rat plasma. Furthermore, the method was applied to investigate the pharmacokinetic characteristics of ZCJ14. Chromatographic separation of ZCJ14 and internal standard (IS) [1-phenyl-3-(4-((3-(trifluoromethyl)phenyl)amino) quinazolin-6-yl)urea] was accomplished by gradient elution using the Kromasil C18 column. The selected reaction monitoring transitions were performed at m/z 507.24→436.18 and 424.13→330.96 for ZCJ14 and IS, resp. The established method was linear over the concentration range of 10–1000 ng mL−1. The intra- and inter-day precisions were < 11.0 % (except for LLOQ which was up to 14.3 %) and the respective accuracies were within the range of 87.5–99.0 %. The extraction recovery and matrix effect were within the range of 88.4–104.5 % and 87.3–109.9 %, resp. ZCJ14 was stable under all storage conditions. The validated method was successfully applied to the pharmacokinetic study of ZCJ14 in rats, and the pharmacokinetic parameters have been determined. The oral bioavailability of ZCJ14 was found to be 46.1 %. Overall, this accurate and reliable quantification method might be useful for other diarylurea moiety-containing drugs.

scholarly journals Determination of sarecycline by UPLC-MS/MS and its application to pharmacokinetic study in rats

2020 ◽  
Author(s):  
Yonghui Shen ◽  
Deru Meng ◽  
Feifei Chen ◽  
Hui Jiang ◽  
Liming Hu ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Chronic Inflammatory Disease ◽  
Linear Calibration ◽  
Limit Of Quantification ◽  
Acquity Uplc ◽  
Intravenous And Oral Administration

AbstractSarecycline is a narrow-spectrum antibiotic for the treatment of acne, which is a chronic inflammatory disease of the hair follicle sebaceous glands. In the study, UPLC-MS/MS was used to establish a rapid and accurate analytical method. The sarecycline was determined with poziotinib as internal standard (IS) in rat plasma. An ACQUITY UPLC HSS T3 column (2.1 × 100 mm, 1.8 μm) could performe chromatographic separation with the mobile phase (methanol: water of 0.1% formic acid) with gradient elution. The ions of target fragment were m/z 488.19→410.14 for sarecycline and m/z 492.06→354.55 for poziotinib, which could quantify the electrospray ionization of positive multiple reaction monitoring (MRM) mode. The linear calibration curve of the concentration range was 1–1,000 ng/mL for sarecycline with a lower limit of quantification (LLOQ) of 1 ng/mL. The mean recovery was between 82.46 and 95.85% for sarecycline and poziotinib in rat plasma. RSD for precision of inter-day and intra-day were between 3.24 and 13.36%, and the accuracy ranged from 105.26 to 109.75%. The developed and validated method was perfectly used in the pharmacokinetic study and bioavailability of sarecycline after intravenous and oral administration in rats.

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.

Pharmacokinetic Study of Main Active Components of Rumex nepalensis Spreng Extract in Rats Plasma by UPLC-MS/MS

2019 ◽  
Vol 15 (4) ◽  
pp. 371-378
Author(s):  
Jin Wang ◽  
Yang Chu ◽  
Xiao Li ◽  
Navaneethakrishnan Polachi ◽  
Xue-ying Yan ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Limit Of Detection ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Active Components ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass ◽  
Acquity Uplc

Background: The Rumex nepalensis Spreng (RNS) is a traditional Chinese medicine containing rich anthraquinones. However, through proper investigation we have found that there were no reports on the pharmacokinetics of RNS extract in rats. </P><P> Objective: We study on the pharmacokinetic behaviors of emodin, chrysophanol and physcion after oral administration of RNS extract in rat to achieve a better understanding of further clinical application and conduct the preparation development of the herb. Methods: In the present study, a sensitive and rapid ultra-fast liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine the three anthraquinones such as chrysophanol, emodin and physcion in rat plasma along with danthron as the internal standard (IS). The analytes and IS were separated on an Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm) by using the mobile phase of water with 3 mM ammonium acetate and acetonitrile as gradient elution at a flow rate of 0.4 mL min -1. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z 253.1 → 225.0 for chrysophanol, 269.0 → 224.9 for emodin, 282.7→ 240.0 for physcion and m/z 239.0 → 211.0 for IS. The limit of detection and lower limit of quantification were both 2 ng mL -1 in rat plasma. Results: Good linearity of this method was obtained in the range of 2-1000 ng mL -1 , and the correlation coefficient was greater than 0.990. According to regulatory guidelines, the established method was fully validated, and the results were within acceptable limits. Conclusion: The validated method was successfully applied into a pharmacokinetic study of orally administered RNS extract in rats.

scholarly journals Development of an UPLC–MS/MS assay to determine psoralidin in rat plasma and its application in a pharmacokinetic study after intragastric administration

2020 ◽  
Vol 32 (4) ◽  
pp. 215-218
Author(s):  
Feng Feng ◽  
Xiunan Jiang ◽  
Jieying Qiu ◽  
Hongyu Wu ◽  
Xiaojun Cai ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Apparent Volume ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Intragastric Administration ◽  
Rat Tissues ◽  
Pharmacokinetic Characteristic

Psoralidin has a variety of pharmacological activities, such as anti-tumor, anti-depressant, and anti-inflammatory activities. This study aims at developing a rapid ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method to determine psoralidin in rat plasma and studying the pharmacokinetic characteristic of psoralidin after intragastric administration of 20 and 40 mg/kg. Alpinetin was used as an internal standard (IS), and the plasma samples were precipitated with acetonitrile. The calibration curves were linear over the range of 0.2–250 ng/mL (R2 = 0.993). The pharmacokinetic parameters were calculated by DAS 3.0. Half-life (t1/2) was 7.2 ± 0.97 h and 7.1 ± 0.27 h for different dosages, respectively. Tmax was 4.2 ± 1.1 h and 4.0 ± 1.1 h for different dosages, respectively. Apparent volume of distribution (Vd) for different dosages was 630.1 ± 168.8 and 600.1 ± 138.8 L/kg, respectively. Clearance (CL) was 105.6 ± 29.2 and 100.6 ± 22.2 L/h/kg for different dosages, indicating that psoralidin was mainly distributed in rat tissues. The pharmacokinetic study provided important information for further clinical application in the treatment of cancer and osteoporosis.

scholarly journals In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method

2021 ◽  
Vol 11 ◽  
Author(s):  
Congrong Tang ◽  
Xiaohui Niu ◽  
Lu Shi ◽  
Huidan Zhu ◽  
Guanyang Lin ◽  
...  
Keyword(s):  
Oral Treatment ◽  
Internal Standard ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Inhibitory Effect ◽  
Rat Plasma ◽  
Ion Source ◽  
Antifungal Drugs ◽  
Tandem Mass

In the current research experiment, a sensitive, precise and rapid bioanalytical approach involving the detection of fedratinib concentrations in rat plasma by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique was optimized and established, and it was employed to describe the changes of fedratinib concentrations after oral treatment with various antifungal drugs (isavuconazole, posaconazole, fluconazole and itraconazole). An Acquity UPLC BEH reverse-phase C18 column (2.1 mm × 50 mm, 1.7 μm) was used for chromatographic separation of fedratinib and bosutinib (as internal standard (IS) in our study) under a linear gradient elution of the mobile phase, which was composed of solution A (acetonitrile) and solution B (water with 0.1% formic acid), along with 0.40 ml/min flow rate. The analyte and internal standard were measured with electrospray ion source in positive ion mode on a XEVO TQS triple quadrupole tandem mass spectrometer. The newly developed UPLC-MS/MS assay displayed enough linearity within the concentration range of 0.5–500 ng/ml for calibration curve. The intra- and inter-day of precision and accuracy were evaluated and validated to meet the requirements for the guidelines of bioanalytical assay. In addition, the findings of matrix effect, recovery, and stability were all within the acceptable limits. The new UPLC-MS/MS method was also successfully applied to characterize the pharmacokinetic changes of fedratinib in rats in the present of different antifungal drugs (such as isavuconazole, posaconazole, fluconazole and itraconazole). It turned out that fluconazole resulted in a prominent inhibitory effect on fedratinib metabolism in rats, followed by treatment with itraconazole and isavuconazole. Therefore, the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors may occur.

scholarly journals Simultaneous quantification of five bioactive 16-deoxybarringtogenol C triterpenoid saponins in rat plasma by HPLC-MS: Application to a pharmacokinetic study after oral administration of Xanthoceras sorbifolia Bunge husks extract

2020 ◽  
Author(s):  
Weiwei Rong ◽  
Zheng Sun ◽  
Yina Guan ◽  
Ran Liu ◽  
Qing Li ◽  
...  
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Liquid Chromatography Mass Spectrometry ◽  
Established Method ◽  
Triterpenoid Saponins ◽  
Terminal Half Life ◽  
Insight Into

AbstractIn this study, a simple and rapid liquid chromatography-mass spectrometry method was developed to simultaneously determinate five 16-deoxybarringtogenol C triterpenoid saponins with the potential of neuroprotection in rat plasma following the oral administration of the Xanthoceras sorbifolia Bunge husks extract. With digoxin as the internal standard, the plasma samples were pre-treated by ethyl acetate-isopropanol (1:1, v/v). The chromatographic separation of the five analytes was performed using a Phenomenex C18 column (250 mm × 4.6 mm, 5.0 mm) with a mobile phase of 0.05% formic acid (A)-acetonitrile (B). The mass spectrometric detection was carried out in the selected ion mode in positive ionization. The extraction recoveries of the five analytes were all over 71.28%. The established method was fully validated in line with the ICH and Food and Drug Administration (FDA) guidelines and successfully applied to the pharmacokinetic study on the five analytes in rat plasma. The terminal half-life (t1/2) of the five analytes was 2.92 ± 0.57, 5.52 ± 1.75, 2.48 ± 0.62, 2.95 ± 0.94, and 2.34 ± 0.81, respectively. This study was purposed to investigate the oral pharmacokinetic parameters and gain an in-depth insight into the reasonable preclinical use of the husks extract derived from X. sorbifolia Bunge.

Simultaneous Determination of Quercitrin, Afzelin, Amentoflavone, Hinokiflavone in Rat Plasma by UFLC–MS-MS and Its Application to the Pharmacokinetics of Platycladus orientalis Leaves Extract

2018 ◽  
Vol 56 (10) ◽  
pp. 895-902 ◽  
Author(s):  
Chen-xiao Shan ◽  
Shu-chen Guo ◽  
Sheng Yu ◽  
Ming-qiu Shan ◽  
Sam Fong Yau Li ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Platycladus Orientalis ◽  
Chromatography Tandem Mass Spectrometry ◽  
Relative Standard ◽  
Liquid Chromatography Tandem Mass

Abstract Leaves of Platycladus orientalis have been used as blood cooling and homeostatic therapy for thousands of years in traditional Chinese medicine. Emerging evidences of modern pharmacology have proved flavonoids as the key elements responsible for the efficacies. However, there has been no report on pharmacokinetic study of the flavonoids from Platycladus orientalis leaves extract. In this study, a sensitive and rapid ultra-flow liquid chromatography-tandem mass spectrometry method was established and validated for the simultaneous determination of amentoflavone, afzelin, hinokiflavone and quercitrin in rat plasma. The four flavonoids and luteolin (internal standard, IS) were recovered from rat plasma by methanol–ethyl acetate (v:v, 50:50). Chromatographic separation was performed on a C18 column with gradient elution. Our results showed that the recoveries from spiked control samples were more than 85% for all analytes and IS. The relative standard deviations of intra-day and inter-day precision were within 15% while the REs ranged from −6.6% to 8.0%. The validated method in this study was successfully applied to pharmacokinetic study in healthy rats after oral administration of P. orientalis leaves extract.

The UPLC-MS/MS Method for Determination of a Novel Enterovirus 71 Inhibitor in Rat Plasma and its Application to Pharmacokinetic Study

2020 ◽  
Vol 16 (2) ◽  
pp. 117-124
Author(s):  
Hai-Qiu Ma ◽  
Chen-Qiang Zuo ◽  
Ye Yuan ◽  
Yu-Pu Zhang ◽  
Xue Wang ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Enterovirus 71 ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Human Enterovirus ◽  
Circulation System ◽  
Pharmacokinetic Parameters ◽  
Active Inhibitor ◽  
Human Enterovirus 71

Background: TJAB1099 is a novel, highly active inhibitor of human enterovirus 71 (HEV71), which is a most commonly found virus leading to Hand-Foot-Mouth Disease (HFMD). However, the TJAB1099 could not be detected in the plasma using a regular HPLC-UV detection during the pharmacokinetic study due to the poor solubility, which in turn limited the release prior to be absorbed by the gastrointestinal tract. Objective: The objectives of the present study were to improve the solubility of TJAB1099 by preparing formulation and develop an Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) method applied to the pharmacokinetic study. Methods: The TJAB1099 was prepared as a phospholipid complex that intends to increase the watersolubility and subsequently improving TJAB1099 exposed in the circulation system. A highly sensitive UPLC-MS/MS method was developed for the pharmacokinetic study, in which the pharmacokinetic parameters were determined following oral and intravenous administration of 5 mg/kg and 1 mg/kg of TJAB1099 in rats, respectively. Results: The precisions for the method were less than 12.8%, while the accuracies were in the range of 90.8 - 98.0% and 96.1 - 99.6% for within-day and between-day, respectively. The mean recoveries for TJAB1099 and terfenadine (internal-standard, IS) were 85.0 ± 5.4% and 92.4 ± 4.1%, respectively. The pharmacokinetic study revealed that the Cmax of TJAB1099 after oral administration can reach 6.84 ± 2.43 ng/mL, while the Tmax is 0.70 ± 0.11 h. The AUC0-12 is 19.81 ± 11.07 µg/mL/h. However, the absorption was poor with an absolute oral bioavailability of 0.62. Conclusion: The UPLC-MS/MS method was successfully applied in the pharmacokinetic study of TJAB1099 in rats.

A Validated LC–MS/MS Method for the Simultaneous Determination of Ticagrelor, Its Two Metabolites and Major Constituents of Tea Polyphenols in Rat Plasma and Its Application in a Pharmacokinetic Study

2021 ◽  
Author(s):  
Ying Xue ◽  
Ziteng Wang ◽  
Weimin Cai ◽  
Xin Tian ◽  
Shuaibing Liu
Keyword(s):  
Simultaneous Determination ◽  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Plasma Concentrations ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Tea Polyphenols ◽  
Bioanalytical Method Validation

Abstract Ticagrelor is recommended for management of patients with acute coronary syndromes. Green tea is one of the most popular beverages in China and around the world. Their concomitant use is unavoidable. In this study, a selective and sensitive liquid chromatography–tandem mass spectrometry method for the simultaneous determination of plasma concentrations of ticagrelor, its two metabolites and four major constituents of tea polyphenols (TPs) in rats was developed for co-administration study of ticagrelor and TPs. Diazepam was used as internal standard (IS). Plasma samples were extracted employing a liquid–liquid extraction technique. Chromatographic separation was carried out on a Kinetex C18 column (2.1 × 75 mm, 2.6 μm) by gradient elution using 0.1% formic acid in water, acetonitrile and methanol. Seven analytes and IS were detected by a mass spectrometer with both positive and negative ionization by multiple reaction monitoring mode. The method was fully validated to be reliable and reproducible in accordance with food and drug administration (FDA) guidelines on bioanalytical method validation. The method was then successfully applied for pharmacokinetic study of ticagrelor, its two metabolites and four major constituents of TPs in rat plasma after oral administration of ticagrelor and tea polyphenol extracts.

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