Development of a UPLC–MS/MS method for determination of a dual EZH1/2 inhibitor UNC1999 in rat plasma

Bioanalysis ◽  
2021 ◽  
Author(s):  
Chunling Zhou ◽  
Aiping He ◽  
Qiang Kang ◽  
Chensen Li ◽  
Tianzhu Liu ◽  
...  
Keyword(s):  
Good Accuracy ◽  
Matrix Effects ◽  
Pharmacokinetic Profile ◽  
Rat Plasma ◽  
Precipitation Method ◽  
Plasma Samples ◽  
Dual Inhibitor ◽  
Accuracy And Precision ◽  
Ionization Mode

Aim: We aimed to establish and validate a simple and sensitive UPLC–MS/MS method for the determination of UNC1999, a dual inhibitor against EZH1 and EZH2 in plasma samples. Materials & methods: UNC1999 in rat plasma was processed with protein precipitation method and then separated on a C18 column and detected under positive ionization mode. The method presented good linearity over the range of 1.0–2000 ng/ml with good accuracy and precision. UNC1999 was absorbed slowly and achieved a maximum concentration of 118.8 ± 12.0 ng/ml 1.5 h after oral administration. Conclusion: The method provides a favorable character in selectivity, linearity, accuracy, precision, recovery, matrix effects and stabilities and was suitable for describing the pharmacokinetic profile of UNC1999.

Development of a ultra-performance LC–MS/MS method for quantification of GW788388 and its applications in pharmacokinetic study in rats

Bioanalysis ◽  
2020 ◽  
Vol 12 (23) ◽  
pp. 1681-1688
Author(s):  
Lina Fang ◽  
Chunling Zhou ◽  
Meihua Jiang ◽  
Xiaoxin Li ◽  
Tianzhu Liu ◽  
...  
Keyword(s):  
Relative Error ◽  
Peak Concentration ◽  
Renal Fibrosis ◽  
Pharmacokinetic Profile ◽  
Rat Plasma ◽  
Precipitation Method ◽  
Quantification Method ◽  
Orally Active ◽  
Tgf Β1

Aim: GW788388 is a selective and orally active TGF-β1 receptor inhibitor that shows potent activity in renal fibrosis. We aimed to establish and validate a simple and sensitive ultra-performance LC–MS/MS method for the determination of GW788388 in plasma samples. Methodology & results: GW788388 in rat plasma was processed with protein precipitation method and then separated on a C18 column. The calibration curve presented a good linearity in the range of 1.0–1200 ng/ml, with satisfactory accuracy (relative error, [-17.5% < relative error <11.7%) and precision (CV <8.9%) for all quality control samples. After oral administration, GW788388 was absorbed quickly and reached a peak concentration of 595.3 ± 60.2 ng/ml after 20 min. Conclusion: The validated method provides a quantification method of GW788388 in rat plasma in detail, and can be utilized to successfully describe the pharmacokinetic profile of GW788388.

scholarly journals Spectrofluorometric Analysis of New-Generation Antidepressant Drugs in Pharmaceutical Formulations, Human Urine, and Plasma Samples

2012 ◽  
Vol 27 ◽  
pp. 59-71 ◽  
Author(s):  
Ruchita S. Das ◽  
Y. K. Agrawal
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Good Accuracy ◽  
Biological Fluids ◽  
Antidepressant Drugs ◽  
Pharmaceutical Formulations ◽  
Plasma Samples ◽  
Limit Of Quantification ◽  
Accuracy And Precision ◽  
New Generation

Spectrofluorometric analysis for the quantification of new-generation antidepressant drugs belong to the class of selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors is described. Five different drugs, sertraline, paroxetine, citalopram, venlafaxine, and fluoxetine, were analysed for spectrofluorometric detection in pharmaceutical formulations and urine and plasma samples. The calibration curves were found linear between fluorescence intensity and drugs concentration in the range of 5–500 ng/L with coefficients of determination above 0.9985 for all the analytes. The method recoveries were higher than 85% in all the three matrices. The intra- and interday variation coefficients were observed less than 8% and 13%, respectively. The limits of detection (LOD) and limit of quantification (LOQ) were found in the range of 0.016–0.084 ng/L and 0.090–0.285 ng/L, respectively. Additionally, the results were compared statistically for each analyte in all the three matrices and were found equivalent, which signifies the absence of matrix effect. Thus, the method will be applied successfully to the determination of the cited drugs in pure or dosage forms as well as in biological fluids with good accuracy and precision.

Investigation of a QuEChERS Based Method for Determination of Polycyclic Aromatic Hydrocarbons in Rat Plasma by GC/MS

2021 ◽  
Author(s):  
Noha F El Azab ◽  
Said F Hotar ◽  
Yossra A Trabik
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Aromatic Hydrocarbons ◽  
Matrix Effects ◽  
Rat Plasma ◽  
Gas Chromatography Mass Spectrometry ◽  
Plasma Samples ◽  
Material Optimization ◽  
Limit Of Quantitation ◽  
Polycyclic Aromatic

Abstract Owing to their toxic effects on humans and the environment, sensitive biomonitoring of polycyclic aromatic hydrocarbons (PAHs) is essential and significant. In this work, a sensitive, simple and rapid bioanalytical method was established for the simultaneous determination of thirteen (PAHs) in rat plasma depending on QuEChERS as a preliminary step and gas chromatography/mass spectrometry (GC/MS) for identification. QuEChERS procedure was optimized where acetonitrile was employed for plasma samples extraction which was further cleaned using primary secondary amine as the sorbent material. Optimization of GC/MS conditions was performed to produce optimum selectivity of the proposed method. The method was fully validated for rat plasma samples where recoveries, matrix effects, limit of quantitation, linearity, and precision were evaluated. Linearity range was 5.0–100.0 ng/mL for most of the thirteen analytes. Average recoveries of the thirteen PAHs ranged between 85.57 % to 109.64 % in fortified rat plasma with standard deviations (SDs) less than 8.91 except for anthracene which showed 19.24. The limits of detection (LODs) and quantitation (LOQs) for the thirteen compounds ranged from 0.045 to 0.372 ppb and from 0.137 to 1.128 ppb respectively. The established method was successfully implemented to perform a minor toxicokinetic study in intraperitoneally dosed rats (0.25 and 2 mg/kg in vegetable oil). The thirteen PAHs were tracked in rat plasma samples for 6 h after administration, and most of the target compounds were recognized in plasma samples only at the higher dose.

Quantitation of vistusertib by UHPLC-MS/MS in rat plasma and its application to a pharmacokinetic study

Bioanalysis ◽  
2021 ◽  
Author(s):  
Fuqi Wang ◽  
Danni Song ◽  
Fengmao Zou ◽  
Honghui Zhao ◽  
Xu Zhao
Keyword(s):  
Oral Administration ◽  
Rat Plasma ◽  
Sprague Dawley ◽  
Rapid Absorption ◽  
Sd Rats ◽  
Accuracy And Precision ◽  
Sprague Dawley Rats ◽  
Ionization Mode ◽  
Pharmacokinetic Behavior

Aim: The present study aimed to develop a UHPLC-MS/MS method for determination of vistusertib in biological matrix, and to describe the pharmacokinetic behavior of vistusertib in SD rats. Methodology & results: After protein precipitation with acetone and acetonitrile (1:1), the chromatographic separation was achieved on an Agilent Poroshell 120 EC-C18 column and detected with a SCIEX QTRAP 4500 mass spectrometer under positive ionization mode. The developed UHPLC-MS/MS method showed an excellent linearity within the range of 1.0–3000 ng/ml with good accuracy and precision. Vistusertib showed a rapid absorption and reached the maximum concentration of 3532.2 ± 678.0 ng/ml 20–30 min after oral administration in Sprague-Dawley rats. Conclusion: The established analytical method was fast, sensitive and robust, and successfully applied to describe the pharmacokinetic behavior of vistusertib following an oral administration in rats.

LC–MS/MS Determination of Apigenin in Rat Plasma and Application to Pharmacokinetic Study

2020 ◽  
Vol 21 ◽  
Author(s):  
Shixing Zhu ◽  
Jiayuan Zhang ◽  
Zhihua Lv ◽  
Mingming Yu
Keyword(s):  
Formic Acid ◽  
Pharmacokinetic Study ◽  
Ammonium Acetate ◽  
Rat Plasma ◽  
Biological Properties ◽  
Plasma Samples ◽  
Supply Rate ◽  
Natural Plant ◽  
Ammonium Acetate Buffer

Background: Apigenin, a natural plant flavone, has been shown to possess a variety of biological properties. Objective: In this report, a highly selective and sensitive LC-MS/MS method was developed and validated for the determination of apigenin in rat plasma. Methods: Analysts were separated on the HSS T3 column (1.8 μm 2.1×100 mm) using acetonitrile and 0.1% formic acid in 2 mM ammonium acetate buffer at a supply rate of 0.200 mL/min as eluent in gradient model. Results: Plasma samples were treated by protein precipitation using acetonitrile for the recovery ranging from 86.5% to 90.1% for apigenin. The calibration curves followed linearity in the concentration range of 0.50-500 ng/mL. The inter-day and intra-day precisions at different QC levels within 13.1% and the accuracies ranged from -10.6% to 8.6%. Conclusion: The assay has been successfully applied to the pharmacokinetic study of apigenin in rats.

Development and Validation of an LC-MS/MS Method for Simultaneous Determination of Canagliflozin and Metformin HCl in Rat Plasma and its Application

2020 ◽  
Vol 16 (6) ◽  
pp. 752-762
Author(s):  
Vivek Nalawade ◽  
Vaibhav A. Dixit ◽  
Amisha Vora ◽  
Himashu Zade
Keyword(s):  
Internal Standard ◽  
Rat Plasma ◽  
Precipitation Method ◽  
Herbal Extracts ◽  
One Step ◽  
Precision And Accuracy ◽  
Development And Validation ◽  
The Impact ◽  
Metformin Hcl

Background: Food and herbal extracts rich in Quercetin (QRT) are often self-medicated by diabetics and can potentially alter the pharmacokinetics (PK) of Metformin HCl (MET) and Canagliflozin (CNG) leading to food or herb-drug interactions and reduced therapeutic efficacy. However, the impact of these flavonoids on the pharmacokinetic behaviour of MET and CNG is mostly unknown. Methods: A simple one-step protein precipitation method was developed for the determination of MET and CNG from rat plasma. The mobile phase chosen was MeOH 65% and 35% water containing 0.1% formic acid at a flow rate of 1mL/min. Results: The retention time of MET, internal standard (Valsartan) and CNG was 1.83, 6.2 and 8.2 min, respectively. The method was found to be linear in the range of 200 - 8000 ng/mL for CNG and 100 = 4000 ng/ml for MET. Precision and accuracy of the method were below 20% at LLOQ and below 15% for LQC, MQC, and HQC. Conclusion: The method was successfully applied for the determination of PK of MET and CNG by using 100 μL of rat plasma. QRT co-administration affects the PK parameters of MET and CNG. This alteration in PK parameters might be of significant use for clinicians and patients.

VALIDATED RP-HPLC AND UV-SPECTROSCOPY METHODS FOR THE ESTIMATION OF DAPAGLIFLOZIN IN BULK AND IN TABLETS

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (03) ◽  
pp. 44-51
Author(s):  
B. Sabbagh ◽  
B. V. S. Lokesh ◽  
G. A. Akouwah ◽  
Keyword(s):  
Good Accuracy ◽  
Uv Spectroscopy ◽  
Linear Regression Analysis ◽  
Molar Absorptivity ◽  
Hplc Method ◽  
Rp Hplc ◽  
Accuracy And Precision ◽  
Significant Difference ◽  
Uv Visible

Two methods were developed for the determination of dapagliflozin (DAPA) in pure form and in tablets. The procedure utilized was UV-Visible Spectroscopy and RP-HPLC with PDA detector to quantify DAPA in bulk and tablets. The sensitive linear range was identified for both methods within 0.5-5.0μg/mL. The linear regression analysis was identified for both methods with correlation coefficient(r)>0.99. The LOD and LOQ values were found to be 0.05 μg/mL and 0.5 μg/mL for the method by UV-Spectroscopy. The molar absorptivity (ε) was calculated as 1.27 X 105 L.mol-1cm-1. The RP-HPLC method produced LOD and LOQ values of 1.0 ng/mL and 0.5 μg/mL. Both methods were simple, precise, reproducible to quantify the amount of unknown in bulk as well as in tablets and estimated accurately within the range of 100.0±0.5%. Statistical analysis was performed on the data obtained. There was no significant difference between the developed and reported methods with p>0.05. Both methods can be applied for routine analysis of DAPA in bulk and tablets with good accuracy and precision.

scholarly journals Uv Spectrophotometric Methods for Determination of Sofosbuvir in Pure Form and Pharmaceutical Dosage Forms in Presence of Its Alkaline Degradate

2020 ◽  
pp. 12-25
Author(s):  
Zeinab Adel Nasr ◽  
Noha S. Said ◽  
Sawsan A. Abdel-Razeq
Keyword(s):  
Good Accuracy ◽  
Dosage Forms ◽  
Difference Spectra ◽  
Pharmaceutical Dosage Forms ◽  
Spectrophotometric Methods ◽  
Good Linearity ◽  
Ratio Difference ◽  
Accuracy And Precision ◽  
Tablet Dosage

Aims: Two spectrophotometric methods were developed and validated for the determination of sofosbuvir in presence of its alkaline degradate. Study Design: Ratio difference and ratio derivative methods were assisted for determination of sofosbuvir in presence of its alkaline degradate, laboratory-prepared mixtures and in tablet dosage forms. Place and Duration of Study: Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy (Girls), Al - Azhar University, between December 2019 and January 2020. Methodology: Two analytical methods were achieved and validated for the quantitative determination of Sofosbuvir in presence of its alkaline degradate. The first method was ratio difference (RD) method, where the UV absorption spectra of different concentrations of sofosbuvir were divided by the spectrum of a certain concentration (15 µg mL-1) as a devisor of its alkaline degradate to get the ratio difference spectra. Afterwards, the peak amplitudes difference between 253.7 and 243.5 nm were measured. The second method was the ratio derivative (1DR) method, where the first derivative of the ratio spectra (1DR) was obtained and its amplitude was measured at 247 and 268 nm. Good linearity was obtained over the concentration range of 3-15 µg mL-1 for the proposed methods. The proposed procedures were adopted for the selective determination of intact Sofosbuvir in presence of up to 80% of its degradation product. Sofosbuvir was exposed to different conditions as alkaline, acidic and oxidative degradation. Results: The proposed methods were developed and validated with good linearity range of 3-15 µg mL-1 for both methods, and also with good accuracy and precision. And the obtained results were statistically compared to those obtained by the reported method. Conclusion: Sofosbuvir was successfully determined by the proposed ratio difference and ratio derivative methods in bulk powder, laboratory prepared mixtures and tablet dosage form with good accuracy and precision. The methods were validated according to ICH guidelines. The results obtained were compared with those of the reported method and were found to be in good agreement.

Simultaneous determination of chito-oligosaccharide in rat plasma by LC-MS/MS method: Application to a pharmacokinetics study

2021 ◽  
Author(s):  
Pengpeng Zhang ◽  
Liu Shuai ◽  
Shuang Yang ◽  
Yuanhong Wang ◽  
Ting-Fu Jiang ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Rat Plasma ◽  
Plasma Samples ◽  
Pharmacokinetics Study ◽  
Sensitive Method

A simple and sensitive method for the simultaneous determination of chito-oligosaccharide (COS) with degrees of polymerization（DPs）from 2 to 7 was developed and used for COS quantification in rat plasma. Samples...

Optimization of selective pressurized liquid extraction and ultrasonication-assisted QuEChERS methods for the determination of polybrominated diphenyl ethers in sediments

2015 ◽  
Vol 7 (22) ◽  
pp. 9542-9548 ◽  
Author(s):  
Shanjun Song ◽  
Xinhua Dai ◽  
Weihua Wang ◽  
Yajuan He ◽  
Zhao Liu ◽  
...  
Keyword(s):  
Polybrominated Diphenyl Ethers ◽  
Good Accuracy ◽  
Liquid Extraction ◽  
Pressurized Liquid Extraction ◽  
Real Samples ◽  
Accuracy And Precision ◽  
Diphenyl Ethers ◽  
Selective Pressurized Liquid Extraction

SPLE and ultrasonication-assisted QuEChERS were optimized for the analysis of PBDEs in sediments. Both methods were validated by SRMs with good accuracy and precision. Real samples were also analyzed and the results showed both methods practicable for PBDEs determination.

Sign in / Sign up

Export Citation Format

Share Document