scholarly journals Eco-Friendly, Simple, Fast, and Sensitive UPLC-MS/MS Method for Determination of Pexidartinib in Plasma and Its Application to Metabolic Stability

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 297
Author(s):  
Essam Ezzeldin ◽  
Muzaffar Iqbal ◽  
Yousif A. Asiri ◽  
Gamal A. E. Mostafa ◽  
Ahmed Y. A. Sayed
Keyword(s):  
Formic Acid ◽  
Method Validation ◽  
Multiple Reaction Monitoring ◽  
Liver Microsomes ◽  
Internal Standard ◽  
Metabolic Stability ◽  
Methyl Tert Butyl Ether ◽  
Butyl Ether ◽  
Limit Of Quantitation

Pexidartinib is the first drug approved by the U.S. Food and Drug Administration specifically to treat the rare joint tumor tenosynovial giant cell tumor. In the current study, a validated, selective, and sensitive UPLC-MS/MS assay was developed for the quantitative determination of pexidartinib in plasma samples using gifitinib as an internal standard (IS). Pexidartinib and IS were extracted by liquid-liquid extraction using methyl tert-butyl ether and separated on an acquity BEH C18 column kept at 40 °C using a mobile phase of 0.1% formic acid in acetonitrile: 0.1% formic acid in de-ionized water (70:30). The flow rate was 0.25 mL/min. Multiple reaction monitoring (MRM) was operated in electrospray (ESI)-positive mode at the ion transition of 418.06 > 165.0 for the analyte and 447.09 > 128.0 for the IS. FDA guidance for bioanalytical method validation was followed in method validation. The linearity of the established UPLC-MS/MS assay ranged from 0.5 to 1000 ng/mL with r > 0.999 with a limit of quantitation of 0.5 ng/mL. Moreover, the metabolic stability of pexidartinib in liver microsomes was estimated.

scholarly journals Quick and simple LC-MS/MS method for the determination of simvastatin in human plasma: application to pharmacokinetics and bioequivalence studies

2014 ◽  
Vol 50 (3) ◽  
pp. 543-550 ◽  
Author(s):  
Suéllen Cristina Rennó Silva ◽  
Gustavo Rodrigues de Rezende ◽  
Vanessa Bergamin Boralli
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Human Plasma ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Methyl Tert Butyl Ether ◽  
Ionization Mass ◽  
Butyl Ether ◽  
Relative Standard

A simple, rapid, and sensitive method based on liquid chromatography-tandem mass spectrometry for the quantitative determination of simvastatin in human plasma was developed and validated. After a simple extraction with methyl tert-butyl ether, the analyte and internal standard (lovastatin) were analyzed using reverse-phase liquid chromatography, on a Kinetex C18column (100 × 4.6 mm, 2.6 μm) using acetonitrile: ammonium acetate (2 mM + 0.025 % formic acid) (70: 30, v/v) as a mobile phase in a run time of 3.5 min. Detection was carried out using electrospray positive ionization mass spectrometry in the multiple-reaction monitoring mode. The method was linear over 0.04-40.0 ng/mL concentration range. The mean extraction recovery of simvastatin was 82% (RSD within 15%). Intraday and interday precisions (as relative standard deviation) were all ≤8,7% with accuracy (as relative error) of ±8%. This rapid and reliable method was successfully applied for a bioequivalence study of 40 mg of simvastatin orally disintegrating tablets in 44 healthy volunteers, showing that this method is suitable for the quantification of simvastatin in human plasma samples for pharmacokinetics and bioequivalence studies.

Simultaneous Determination of Four Herbicide and Pesticide Residues in Chinese Green Tea Using QuEChERS Purification Procedure and UPLC-MS/MS Analysis

2013 ◽  
Vol 634-638 ◽  
pp. 1586-1590
Author(s):  
Su Fang Wang ◽  
Shou Jie Zhang ◽  
Chun Hong Dong ◽  
Guo Qing Wang ◽  
Jun Feng Guo ◽  
...  
Keyword(s):  
Formic Acid ◽  
Simultaneous Determination ◽  
Green Tea ◽  
Limit Of Detection ◽  
Multiple Reaction Monitoring ◽  
Graphitized Carbon Black ◽  
Ms Analysis ◽  
Relative Standard ◽  
Limit Of Quantitation

A method for simultaneous determination of residuals of four herbicides and pesticides, simazine, carboxin, diflubenzuron and rotenone, in Chinese green tea was developed. In the proposed method, the tea powder was placed in a centrifuge tube with a plug, extracted in saturated aqueous sodium chloride solution and acetonitrile, agitated using vortex oscillator, and then centrifuged 5 min at 4000 rpm. The supernatant solution was purified by primary secondary amine (PSA) sorbent, C18 power, and graphitized carbon black powder, respectively. Then the purified extracts were dissolved with acetonitrile:0.1% formic acid aqueous solution (40:60, V/V) and agitated, filtered using a syringe with 0.22 μm nylon filter prior to UPLC-MS/MS analysis. The UPLC analysis was performed on an ACQUITY UPLC® HSS T3 column (2.1 mm×100 mm, 1.8 µm), using acetonitrile-0.1% formic acid as mobile phase with the flow rate as 0.3 mL•min-1. Injection volume was 10 µL. Positive ionization mode was applied, and the ions were monitored in the multiple reaction monitoring (MRM) mode with curtain gas 0.069 MPa, collision gas 0.052 MPa, ESI ion spray voltage 5000 V, temperature 550 °C, nebulizer gas 0.24 MPa, and turbo gas 0.28 MPa. The limit of detection (LOD) and limit of quantitation (LOQ) of the proposed method are 1 μg•kg-1and 5 μg•kg-1, respectively. The average recoveries of the four pesticides at 10, 20, and 50 µg•kg-1spiking levels range from 77.4% to 95.3%. TheSupersSuperscript textcript textrelative standard deviation (RSD) (n=6) range form 11.83% to 4.52%.

Rapid determination of patulin in medicinal hawthorn fruits by HPLC-MS/MS

2012 ◽  
Vol 5 (1) ◽  
pp. 31-36 ◽  
Author(s):  
L. Xiang ◽  
Y. Gao ◽  
D. Liu ◽  
M. Yang
Keyword(s):  
Rapid Determination ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Negative Ion ◽  
Liquid Liquid Extraction ◽  
Relative Standard ◽  
Limit Of Quantitation ◽  
Hawthorn Fruit ◽  
Negative Ion Mode

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.

Development and Validation of Novel UPLC-MS/MS Method for the Analysis of Macitentan in Pharmaceutical Formulations

2019 ◽  
Vol 15 (5) ◽  
pp. 554-559
Author(s):  
Mevlut Albayrak ◽  
Alptug Atila
Keyword(s):  
Atmospheric Pressure Chemical Ionization ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Pharmaceutical Preparations ◽  
Pharmaceutical Formulations ◽  
Ultra Performance Liquid Chromatography ◽  
Pure Form ◽  
Column Temperature ◽  
Limit Of Quantitation

Introduction: Macitentan is an endothelin receptor antagonist drug used in the treatment of pulmonary arterial hypertension. Materials and Methods: A new, sensitive, simple, accurate and rapid ultra-performance liquid chromatography in combination with tandem triple quadruple mass spectrometry (UPLC-MS/MS) method has been developed and validated for the determination of macitentan in pharmaceutical formulations. Macitentan and bosentan which are used as internal standard (IS) were detected using atmospheric pressure chemical ionization (APCI) in positive ion, multiple reaction monitoring (MRM) mode by monitoring mass transitions (precursor to product) m/z 589.1→203.3 and 552.6→311.5, respectively. Chromatographic separation was carried out on reverse phase C18 column (5 µm, 4.6 * 150 mm). Water containing 0.2 % acetic acid in acetonitrile (10:90, v/v) was used as the mobile phase in the isocratic elution. The system was optimized with injection volume of 10 µL, column temperature of 35 °C and flow rate of 1 mL min-1 Retention times were 1.97 min for macitentan and 1.72 min for IS. Results and Discussion: The calibration curve with a high correlation coefficient (0.9997) was linear range 0.5-500 ng mL-1. The lower limit of quantitation (LLOQ) and average recovery values were determined as 0.5 ng mL-1 and 99.7 %, respectively. The developed novel method has been successfully applied for the determination of macitentan in pure form and pharmaceutical formulations. Conclusion: The present method is the first study developed and validated for the determination of macitentan from the pharmaceutical preparations and pure form by UPLC-MS/MS method in the literature.

Development and Validation of Liquid Chromatography-mass Spectrometry Method for the Determination of Intracellular Concentration of Ginkgolide A, B, C, and Bilobalide in Transporter-Expressing Cells

2020 ◽  
Vol 16 (6) ◽  
pp. 763-773
Author(s):  
Peter Yaro ◽  
Jing Nie ◽  
Mingcheng Xu ◽  
Kui Zeng ◽  
Su Zeng
Keyword(s):  
Ascorbic Acid ◽  
Matrix Effect ◽  
Multiple Reaction Monitoring ◽  
Organic Cation Transporter ◽  
Cellular Systems ◽  
Negative Ion ◽  
Methyl Tert Butyl Ether ◽  
Butyl Ether ◽  
Ginkgolide A

Background: Terpene lactones are major components of ginkgo biloba extract which are used in cardiovascular and degenerative diseases. To study the involvement of transporters in the transport/disposition of ginkgolides A, B, C, and bilobalide, a bioanalytical assay was developed by LCMS/ MS system for the quantitation of intracellular levels of terpene lactones in cells expressing organic cation transporter 2 (OCT2). Methods: The assay involved an optimized simple sample handling with methyl tert-butyl ether for liquid-liquid extraction and reconstitution in modified dissolution solution. Pretreatment of samples with 50 μM ascorbic acid and the addition of ascorbic acid and formic acid in dissolution solution significantly reduced matrix effect and stabilized the postpreparative samples. Separations were performed by Zobrax RRHD column (extend-C18 1.8μm, 3.0 x 100mm) and acetonitrile gradient elution. The analysis was carried out in the negative ion scan mode using multiple reaction monitoring. Results: The method was validated for linearity (concentration range of 20-5000nM), accuracy (±13.1%), precision (<11.0%), recovery (94.31–105.9%), matrix effect (93.8-111.0%) and stability. Finally, the method was applied in the determination of intracellular concentrations of ginkgolides A, B, C, and bilobalide in Madin-Darby canine kidney (MDCK-mock) and MDCK-OCT2 cells in uptake study. Conclusion: The developed method was successfully validated. Results suggest that OCT2 is involved in the renal disposition of ginkgolide A, B, and bilobalide. This method would foster the study of transport mediated activity via the interaction of ginkgolides and bilobalide with cellular systems.

A Comparative Pharmacokinetic Study of Schisandrol B After Oral Administration of Schisandrol B Monomer and Schisandra chinensis Extract

2019 ◽  
Vol 16 ◽  
Author(s):  
Zijing Wu ◽  
Dahu Liang ◽  
Maodi Xu ◽  
Yanhao Liu ◽  
Haitang Xie
Keyword(s):  
Oral Administration ◽  
Formic Acid ◽  
Multiple Reaction Monitoring ◽  
The Body ◽  
Methyl Tert Butyl Ether ◽  
Pharmacokinetic Parameters ◽  
Schisandra Chinensis ◽  
Sprague Dawley ◽  
Butyl Ether ◽  
Multiple Reaction Monitoring Mode

Background: Schisandra chinensis Turcz. (Baill.) is a perennial deciduous woody vine plant that is beneficial to all systems of the body. Objective: The goals of the present study were to compare the pharmacokinetics of schisandrol B in rats after oral administration of schisandrol B monomer (10 mg/kg) and S. chinensis extract (equivalent to 10 mg/kg schisandrol B) and to explore interactions among the components in S. chinensis extract. Method: Twelve Sprague-Dawley rats of SPF grade were randomly divided into the monomer and S.chinensis extract groups. Plasma samples were extracted with methyl tert-butyl ether, and chromatographic separation was performed on an Agilent ZORBAX Eclipse XDB-C18 (4.6 × 150 mm, 5 μm) column with the mobile phase consisting of methanol (containing 0.1% formic acid)-water (containing 0.1% formic acid and 5 mmol ammonium acetate). This analysis was achieved by multiple reaction monitoring mode in an electrospray interface. Results: The seven lignans had good linear relationship within the determination range (r>0.9950); the intra- and inter-day precision were < 12.08% and accuracy was 88.64%-111.61%. The pharmacokinetic parameters (T1/2, Tmax, MRT0-∞, CL, AUC0-t, and AUC0-∞) of schisandrol B showed significant differences between the two groups (P < 0.05). Conclusion: The validated method has been successfully applied to the pharmacokinetics of schisandrin, schisandrol B, schisandrin A, schisandrin B, schisandrin C, schisanhenol, and schisantherin A. The pharmacokinetic differences indicate that other components in the extract may increase the absorption of schisandrol B, decrease the rate of elimination, and improve the bioavailability of schisandrol B.

scholarly journals A Validated HPLC-MS/MS Method for Simultaneous Determination of Militarine and Its Three Metabolites in Rat Plasma: Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Hui-Yuan Sun ◽  
Lin Zheng ◽  
Zi-Peng Gong ◽  
Yue-Ting Li ◽  
Chang Yang ◽  
...  
Keyword(s):  
Formic Acid ◽  
Simultaneous Determination ◽  
Multiple Reaction Monitoring ◽  
Area Under The Curve ◽  
Internal Standard ◽  
Rat Plasma ◽  
Relative Standard ◽  
Method Accuracy

A rapid, reliable, and sensitive HPLC-electrospray ionization-tandem mass spectrometry (HPLC-MS/MS) method was established and validated for simultaneous determination of militarine and its three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) in rat plasma. Plasma was acidified with formic acid, and protein was precipitated with methanol. MS/MS with ESI and multiple reaction monitoring at m/z 725.3→457.3, 457.1→127, 304.3→107.2, 189→129, and 417.1→267.1 was used for determination of militarine, gastrodin, α-isobutylmalic acid, gymnoside I, and puerarin (internal standard), respectively. Chromatographic separation was conducted using an ACE UltraCore SuperC18 (2.1 × 100 mm, 2.5 μm) column with gradient mobile phase (0.1% formic acid in water and acetonitrile). The lower limits of quantitation for militarine, gastrodin, α-isobutylmalic acid, and gymnoside I were 1.02, 2.96, 1.64, and 0.3 ng/mL, respectively. The relative standard deviations of intra- and interday measurements were less than 15%, and the method accuracy ranged from 87.4% to 112.5%. The extraction recovery was 83.52%-105.34%, and no matrix effect was observed. The three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) were synchronously detected at 0.83 h, suggesting that militarine was rapidly transformed to gastrodin, α-isobutylmalic acid, and gymnoside I. Moreover, the area under the curve (AUC) and Cmax of militarine were significantly lower than those of gastrodin and α-isobutylmalic acid, showing that militarine was largely metabolized to gastrodin and α-isobutylmalic acid in vivo. The studies on pharmacokinetics of militarine and its three metabolites were of great use for facilitating the clinical application of militarine and were also highly meaningful for the potential development of militarine.

scholarly journals NEW METHOD DEVELOPMENT AND VALIDATION FOR THE DETERMINATION OF FEBUXOSTAT IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY–MASS SPECTROMETRY

2016 ◽  
Vol 8 (9) ◽  
pp. 61 ◽  
Author(s):  
Narottam Pal ◽  
Avanapu Srinivasa Rao ◽  
Pigilli Ravikumar
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Human Plasma ◽  
Method Development ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
New Method ◽  
Liquid Chromatography Mass Spectrometry ◽  
Chromatography Mass Spectrometry

<p><strong>Objective</strong>:<strong> </strong>To develop a new method and validate the same for the determination of Febuxostat (FBS) in human plasma by liquid chromatography–mass spectrometry (LCMS).</p><p><strong>Methods</strong>:<strong> </strong>The present method utilized reversed-phase high-performance liquid chromatography with tandem mass spectroscopy. Febuxostat D9 (FBS D9) was used as internal standard (IS). The analyte and internal standard were separated from human plasma by using solid phase extraction method. Zorbax Eclipse XDB, C<sub>8</sub>, 100 mm x 4.6 mm, 3.5 µm column was used and HPLC grade acetonitrile, 5 millimolar (mM) ammonium format (80: 20, v/v) as mobile phase, detected by mass spectrometry operating in positive ion and multiple reaction monitoring modes.</p><p><strong>Results</strong>:<strong> </strong>The parent and production transitions for FBS and internal standard were at m/z 317.1→261.0 and 326.1→262.0 respectively. The method was validated for system suitability, specificity, carryover effect, linearity, precision, accuracy, matrix effect, sensitivity and stability. The linearity range was from 20.131 ng/ml to10015. 534 ng/ml with a correlation coefficient of 0.999. Precision results (%CV) across six quality control samples were within the limit. The percentage recovery of FBS and internal standard from matrix samples was found to be 76.57% and 75.03% respectively.</p><p><strong>Conclusion</strong>:<strong> </strong>Present study describes new LC-MS method for the quantification of FBS in a pharmaceutical formulation. According to validation results, it was found to be a simple, sensitive, accurate and precise method and also free from any kind of interference. Therefore the proposed analytical method can be used for routine analysis for the estimation of FBS in its formulation.</p>

scholarly journals UHPLC-QQQ-MS/MS assay for quantification of dianthrones as potential toxic markers of Polygonum multiflorum Thunb: Application to the standardization of TCMs with endogenous toxicity

2021 ◽  
Author(s):  
Jian-Bo Yang ◽  
Yun-Fei Song ◽  
Yue Liu ◽  
Hui-Yu Gao ◽  
Qi Wang ◽  
...  
Keyword(s):  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Triple Quadrupole ◽  
Quadrupole Mass ◽  
Polygonum Multiflorum ◽  
Triple Quadrupole Mass Spectrometer ◽  
Benefit Risk Assessment ◽  
Heparg Cells

Abstract Background: The raw and processed roots of Polygonum multiflorum Thunb (PM) are commonly used in clinical practice to treat diverse diseases; however, the reports of hepatotoxicity induced by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have emerged worldwide. Thus, it is necessary for researcher to explore the methods to improve its quality standards and further ensure its quality and treatment effect.Methods: In the present study, an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QQQ- MS/MS) method has been optimized and validated for the determination of dianthrones in PMR and PMRP, using bianthronyl as the internal standard. Chromatographic separation with a gradient mobile phase (A: acetonitrile and B: water containing 0.1% formic acid (v/v)) at a flow rate of 0.25 mL/min was achieved on a Waters Acquilty UPLC BEH b) C18 column (2.1 mm × 50 mm, 1.7 µm). A triple quadrupole mass spectrometer (TQMS) was operated in negative ionization mode with multiple reaction monitoring for the quantitative analysis of six dianthrones. Meanwhile, compounds 5 and 6 were further evaluated for cytotoxicity of HepaRG cells by CCK8 assay.Results: The UHPLC-QQQ-MS/MS method was first developed to simultaneous determination of six dianthrones in PMR and PMRP, namely polygonumnolides C1–C4 (1–4), trans-emodin dianthrones (5), and cis-emodin dianthrones (6). The contents of 1~6 in 90 batches of PMR were in the range of 0.027-19.04, 0.022-13.86, 0.073 -15.53, 0.034 -23.35, 0.38-83.67 and 0.29 -67.00 µg/g, respectively. The contents of 1~6 in 86 batches of commercial PMRP were in the range of 0.020-13.03, 0.051-8.94, 0.022-7.23, 0.030 -12.75, 0.098-28.54 and 0.14-27.79 µg/g, respectively. The six dianthrones were almost completely gone after reasonable processing for 24 h. Meanwhile, compounds 5 and 6 showed the inhibitory activity against HepaRG cells with the IC50 values of 10.98 and 15.45 μM, respectively. Furthermore, a systematic five-step strategy to realize the standardization of TCMs with endogenous toxicity is proposed for the first time, involving the establishment of determination methods, determination of the toxic markers, the standardization of processing method, the development of limit standards and benefit-risk assessment.Conclusion: The results of cytotoxicity evaluation of dianthrone indicated that trans-emodin dianthrones (5) and cis-emodin dianthrones (6) could be selected as the toxic markers of PMRP. Taking PMR and PMRP for example, we hope this study provided insight into the standardization and internationalization of endogenous toxic TCMs, with the main purpose of improving public health by scientifically using TCMs to treat diverse complex diseases in future.

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