scholarly journals Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Bo Li ◽  
Min Lu ◽  
Lei Jin ◽  
Maoen Zheng ◽  
Peilu Sun ◽  
...  
Keyword(s):  
High Performance ◽  
Brain Homogenate ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Brain Distribution ◽  
Single Oral Administration ◽  
Mass Spectrometric Detector ◽  
Distribution Studies ◽  
Lower Limits

Brigatinib and brigatinib-analog are potent and selective ALK inhibitors with the similar structure. A simple and sensitive high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of brigatinib and brigatinib-analog in rat plasma and brain homogenate was developed and validated. Chromatographic separation was carried out on an ODS column with acetonitrile and 0.1% formic acid in water as the mobile phase with gradient elution at a flow rate of 0.5 mL/min. Detections were performed using a TSQ Quantum Ultra mass spectrometric detector with electrospray ionization (ESI) interface, which was operated in the positive ion mode. A simple protein precipitation preparation process was used. The lower limits of quantification (LLOQs) were 1.0 ng/mL and 0.5 ng/mL for analytes in rat plasma and brain homogenate, respectively. The intrabatch and interbatch precision and accuracy of brigatinib and brigatinib-analog were well within the acceptable limits of variation. The simple and sensitive LC-MS/MS method was successfully applied to the pharmacokinetic and brain distribution studies following a single oral administration of brigatinib and brigatinib-analog to rats. The above studies would lay a good foundation for the further applications of brigatinib and brigatinib-analog.

Pharmacokinetics and brain distribution studies of 6-hydroxykynurenic acid and its structural modified compounds

2021 ◽  
Author(s):  
Zhuowei Shen ◽  
Haihong Hu ◽  
Jie Pan ◽  
Mingcheng Xu ◽  
Fengting Ou ◽  
...  
Keyword(s):  
Oral Administration ◽  
Brain Homogenate ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Isopropyl Ester ◽  
Brain Distribution ◽  
Apparent Permeability ◽  
Apparent Permeability Coefficient ◽  
Distribution Studies ◽  
The Brain

Abstract Objectives 6-Hydroxykynurenic acid (6-HKA) is an organic acid component in extracts of Ginkgo biloba leaves and acts as a major contributor to neurorestorative effects, while its oral bioavailability was low. Therefore, using prodrug method to improve the bioavailability and brain content of 6-HKA is significant. Methods Three structural modified compounds of 6-HKA were synthesized, and ultra performance liquid chromatography-tandem mass spectrometry methods for quantification of these structural modified compounds in rat plasma and rat brain homogenate were established and comprehensively validated. The methods were effectively applied to investigate the effects of structural modification on apparent permeability coefficients in cells, the pharmacokinetics and the brain distribution in rats. Key findings The results illustrated that esterification can greatly improve the apparent permeability coefficient and bioavailability of 6-HKA. Comparing with direct oral administration of 6-HKA, the bioavailability of isopropyl ester was greatly improved (from 3.96 ± 1.45% to 41.8 ± 15.3%), and the contents of 6-HKA in rat brains (49.7 ± 9.2 ng/g brain) were significantly higher after oral administration. Conclusions The bioavailability and the brain content of 6-HKA can be improved by the prodrug method. Among three structural modified compounds, isopropyl-esterified 6-HKA was the most promising treatment.

scholarly journals DETERMINATION OF 5H-BENZO[2,3][1,4]OXAZEPINO[5,6-B]INDOLES IN RAT PLASMA BY REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC-ULTRAVIOLET METHOD: APPLICATION TO PHARMACOKINETIC STUDIES

2017 ◽  
Vol 10 (12) ◽  
pp. 425 ◽  
Author(s):  
Ashok K Singh ◽  
Vinit Raj ◽  
Amit Rai ◽  
Amit K Keshari ◽  
Pranesh Kumar ◽  
...  
Keyword(s):  
High Performance ◽  
Gradient Elution ◽  
High Performance Liquid Chromatographic ◽  
Rat Plasma ◽  
Reversed Phase ◽  
Pharmacokinetic Studies ◽  
Relative Standard ◽  
Liquid Chromatographic

Objective: Recently, we reported newly synthesized 5H-benzo[2,3][1,4]oxazepino[5,6-b]indole) derivatives and proved their cytotoxicity against hepatocellular carcinoma specific Hep-G2 cell lines. We attempted herein to describe a reversed-phase high-performance liquid chromatographic method for the determination of three most active compounds 6a, 10a, and 15a in rat plasma to predict their pharmacokinetics parameters before in vivo study.Methods: A rapid and sensitive reversed-phase high-performance liquid chromatographic was employed for the determination of 6a, 10a, and 15a in rat plasma. Each compound was separated by a gradient elution of acetonitrile and water with 1 mL/min flow rate. The detector was set at 270, 285, and 275 nm for 6a, 10a, and 15a and the recorded elution times were 2.00, 2.87, and 1.88 min, respectively.Results: The calibration curve was linear with R2 of 0.938, 0.875, and 0.923 over the concentration range of 0.1–50 μg/mL. The inter- and intra-day variations of the assay were lower than 12.26%; the average recovery of 6a, 10a, and 15a was 97.31, 92.56, and 95.23 % with relative standard deviation of 2.12%, 3.25%, and 2.28%, respectively. The Cmax and Tmax were ~ 46.34, 18.56, and 25.65 μg/mL and 2.0, 4.0, and 4.0 h for 6a, 10a, and 15a, respectively, which indicate a robust method of detection in the present experiment.Conclusion: The study suggests that all of the three compounds have a lower rate of absorption, higher volume of distribution, and lower clearance rate, indicating good therapeutic response for in vivo activity. 

scholarly journals Simultaneous Quantification of Four Ginsenosides in Rat Plasma and Its Application to a Comparative Pharmacokinetic Study in Normal and Depression Rats Using UHPLC-MS/MS

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Lian-yun Du ◽  
Tao Jiang ◽  
Kun Wei ◽  
Shuang Zhu ◽  
Yan-long Shen ◽  
...  
Keyword(s):  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Comparative Pharmacokinetic ◽  
Ginsenoside Rd ◽  
Liquid Chromatography Tandem Mass ◽  
Ginsenoside Rc ◽  
Lower Limits

A sensitive method has been developed for simultaneous determination of ginsenoside Rh1 (G-Rh1), ginsenoside Rb1 (G-Rb1), ginsenoside Rc (G-Rc), and ginsenoside Rd (G-Rd) in rat plasma of normal and depression model group after oral administration of their solutions by using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-QQQ-MS). The biological samples were prepared by protein precipitation. Ginsenoside Rg3 (G-Rg3) was used as an internal standard (IS). MS analysis was performed under the multiple reaction monitoring (MRM) with electron spray ionization (ESI) operated in the negative mode. The method showed good linearity over a wide concentration range (R2 > 0.999) and obtained lower limits of quantification (LLOQ) of 5 ng/mL. The whole analysis procedure could be completed in as short as 16.5 min. The intraday precisions, interday precisions, and stabilities were less than 10%. The extraction recoveries from rat plasma were exceeded 86.0%. The results indicated that there were significant differences between the two groups on pharmacokinetics parameters; the absorptions of four analytes in the depression group were higher than those in the normal group because the liver metabolism and internal environment of the model rats had been affected.

Simultaneous Determination of Eight Potential Q-Markers in Zishen Tongguan Capsules Based on UHPLC-MS/MS

2020 ◽  
Vol 17 (1) ◽  
pp. 47-56
Author(s):  
Shun Liu ◽  
Xun Wang ◽  
Kaiping Zou ◽  
Wei Liu ◽  
Cunyu Li ◽  
...  
Keyword(s):  
Quality Control ◽  
Chinese Medicine ◽  
Simultaneous Determination ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Quality Markers ◽  
High Repeatability ◽  
Comprehensive Study

Background: Zishen Tongguan (ZSTG) capsules were prepared at the Affiliated Hospital of Nanjing University of Chinese Medicine and have been proven to be clinically effective for treating pyelonephritis and benign prostatic hyperplasia. However, the quality standards are not ideal; a comprehensive study of the “quality markers” (Q-markers), the chemicals inherent in traditional Chinese medicine and its preparations, has not been carried out. Experimental Methods: In this paper, a sensitive and specific ultra-high-performance liquid chromatographictandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of eight potential Q-markers of ZSTG, including timosaponin A3, berberine, jatrorrhizine, phellodendrine, palmatine, mangiferin, neomangiferin, and timosaponin BII. A Kromasil 100-3.5 C18 column was used with a mobile phase of 0.2% formic acid with acetonitrile, and gradient elution at a flow rate of 0.2 mL/min was achieved in 13 minutes and used for separation. Detection was performed in positive/negative mode with multiple reaction monitoring (MRM). Results: The analytical method was validated in terms of the sensitivity, linearity, accuracy, precision, repeatability, stability and recovery. The method established here was successfully applied to study the potential Q-markers in 8 batches of commercial samples, which demonstrated its use in improving the quality control of ZSTG. Conclusion: The developed method had high repeatability and accuracy and was suitable for the simultaneous analysis of multiple Q-markers, which may provide a new basis for the comprehensive assessment and overall quality control of ZSTG.

Quantitative Analysis of 5-Hydroxymethylfurfural in Linezolid Injection by High Performance Liquid Chromatography

2020 ◽  
Vol 16 (8) ◽  
pp. 1059-1067
Author(s):  
Jéssica Maurício Batista ◽  
Christian Fernandes
Keyword(s):  
High Performance ◽  
Potassium Phosphate ◽  
Gradient Elution ◽  
High Performance Liquid Chromatographic ◽  
Official Method ◽  
Ph Variation ◽  
Drug Products ◽  
Liquid Chromatographic Method ◽  
Liquid Chromatographic

Background: Linezolid is a synthetic broad-spectrum antibacterial belonging to the class of oxazolidinones. Linezolid for intravenous infusion is isotonized with dextrose. In acidic environment, the dehydration of dextrose produces furan derivatives, 5-hydroxymethylfurfural (5-HMF) being the main one. The determination of this degradation product is of fundamental importance, since there is evidence it is cytotoxic, genotoxic, mutagenic and carcinogenic. However, there is no official method for the determination of 5-HMF in drug products. Objective: The aim of this study was to develop and validate a high performance liquid chromatographic method to quantify 5-HMF in injection of linezolid. Methods: The chromatographic separation, after optimization, was performed on C18 (150 x 4.6 mm, 5 μm) column. Mobile phase was composed of 14 mM potassium phosphate buffer pH 3.0 ([H+] = 1.0 x 10-3) and methanol in gradient elution at 1.0 mL min-1. The injection volume was 10 μL and detection was performed at 285 nm. Results: The method was optimized and validated, showing selectivity, linearity in the range from 0.075 to 9.0 μg mL-1, precision (RSD ≤ 2.0%), accuracy (mean recovery of 100.07%) and robustness for temperature and pH variation. Conclusion: The method was shown to be adequate to determine 5-HMF in injection containing linezolid in routine analysis.

Simultaneous Determination of Six Components in Jingzhiguanxin Tablet by High-Performance Liquid Chromatography

2019 ◽  
Vol 15 (2) ◽  
pp. 130-137
Author(s):  
Hui Jiang ◽  
Lianhao Fu ◽  
Yu Wang ◽  
Shaozhi Wang ◽  
Xiaoxu Zhang ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Gradient Elution ◽  
Tanshinone Iia ◽  
Array Detector ◽  
Control Analysis ◽  
Active Components ◽  
Quality Control Analysis

Background: Jingzhiguanxin (JZGX) tablet, a traditional Chinese prescription, is commonly used for treating coronary heart disease and angina pectoris in the clinic. There are six active components (Danshensu (DSS), Protocatechuic aldehyde (PD), Paeoniflorin (PF), Ferulic acid (FA), Salvianolic acid B (Sal B) and Tanshinone IIA (TA)) in JZGX tablet. </P><P> Objective: In this paper, a simple and reliable method was used for simultaneous determining the six active components by high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Methods: These six active components were separated on an Agilent Zorbax Eclipse XDB-C18 column (150 mmx4.6 mm, 5 µm) at 30 °C. Acetonitrile (A), methanol (B) and 0.5% H3PO4 aqueous solution (C) were used as mobile phase for gradient elution. The flow rate was 1 mL/min and the detection wavelengths were set at 280 nm for DSS, PD and Sal B, 230 nm for PF, 320 nm for FA and 270 nm for TA, respectively. Results: All of the six components showed good linearity regressions (r2≥0.9997) in the detected concentration range. The recovery rates and coefficient of variation (CV) for all analytes were 98.66%- 100.18% and 0.75%-1.89%, respectively. This method was successfully applied to simultaneously determine the six components in JZGX tablet from different batches and manufacturers. Conclusion: The validated method can be used in routine quality control analysis of JZGX tablet without any interference.

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

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.

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