A further study on the combined use of internal standard and isotope-labeled derivatization reagent for expansion of linear dynamic ranges in liquid chromatography–electrospray mass spectrometry

2006 ◽  
Vol 20 (10) ◽  
pp. 1049-1055 ◽  
Author(s):  
Yuhki Tsukamoto ◽  
Tomofumi Santa ◽  
Hiroo Yoshida ◽  
Hiroshi Miyano ◽  
Takeshi Fukushima ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Electrospray Mass Spectrometry ◽  
Internal Standard ◽  
Linear Dynamic ◽  
Combined Use

scholarly journals Quantification of plasma remdesivir and its metabolite GS-441524 using liquid chromatography coupled to tandem mass spectrometry. Application to a Covid-19 treated patient

2020 ◽  
Vol 58 (9) ◽  
pp. 1461-1468 ◽  
Author(s):  
Jean-Claude Alvarez ◽  
Pierre Moine ◽  
Isabelle Etting ◽  
Djillali Annane ◽  
Islam Amine Larabi
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Half Life ◽  
Limit Of Detection ◽  
Treated Patient ◽  
Internal Standard ◽  
Therapeutic Drug ◽  
Active Metabolites ◽  
Limit Of Quantification ◽  
Positive Mode

AbstractObjectivesA method based on liquid chromatography coupled to triple quadrupole mass spectrometry detection using 50 µL of plasma was developed and fully validated for quantification of remdesivir and its active metabolites GS-441524.MethodsA simple protein precipitation was carried out using 75 µL of methanol containing the internal standard (IS) remdesivir-13C6 and 5 µL ZnSO4 1 M. After separation on Kinetex® 2.6 µm Polar C18 100A LC column (100 × 2.1 mm i.d.), both compounds were detected by a mass spectrometer with electrospray ionization in positive mode. The ion transitions used were m/z 603.3 → m/z 200.0 and m/z 229.0 for remdesivir, m/z 292.2 → m/z 173.1 and m/z 147.1 for GS-441524 and m/z 609.3 → m/z 206.0 for remdesivir-13C6.ResultsCalibration curves were linear in the 1–5000 μg/L range for remdesivir and 5–2500 for GS-441524, with limit of detection set at 0.5 and 2 μg/L and limit of quantification at 1 and 5 μg/L, respectively. Precisions evaluated at 2.5, 400 and 4000 μg/L for remdesivir and 12.5, 125, 2000 μg/L for GS-441524 were lower than 14.7% and accuracy was in the [89.6–110.2%] range. A slight matrix effect was observed, compensated by IS. Higher stability of remdesivir and metabolite was observed on NaF-plasma. After 200 mg IV single administration, remdesivir concentration decrease rapidly with a half-life less than 1 h while GS-441524 appeared rapidly and decreased slowly until H24 with a half-life around 12 h.ConclusionsThis method would be useful for therapeutic drug monitoring of these compounds in Covid-19 pandemic.

scholarly journals Determination of synthetic ferric chelates used as fertilizers by liquid chromatography-electrospray/mass spectrometry in agricultural matrices

2007 ◽  
Vol 18 (1) ◽  
pp. 37-47 ◽  
Author(s):  
Ana Álvarez-Fernández ◽  
Irene Orera ◽  
Javier Abadía ◽  
Anunciación Abadía
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Electrospray Mass Spectrometry

scholarly journals Calcineurin Activity Assay Measurement by Liquid Chromatography–Tandem Mass Spectrometry in the Multiple Reaction Monitoring Mode

2014 ◽  
Vol 60 (2) ◽  
pp. 353-360 ◽  
Author(s):  
Lynn Carr ◽  
Anne-Laure Gagez ◽  
Marie Essig ◽  
François-Ludovic Sauvage ◽  
Pierre Marquet ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Mononuclear Cells ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Reaction Monitoring ◽  
Activity Assay ◽  
Peripheral Blood Mononuclear ◽  
Blood Concentrations ◽  
Transplant Patients

Abstract BACKGROUND Blood concentrations of the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus are currently measured to monitor immunosuppression in transplant patients. The measurement of calcineurin (CN) phosphatase activity has been proposed as a complementary pharmacodynamic approach. However, determining CN activity with current methods is not practical. We developed a new method amenable to routine use. METHODS Using liquid chromatography–multiple reaction monitoring mass spectrometry (LC-MRM-MS), we quantified CN activity by measuring the dephosphorylation of a synthetic phosphopeptide substrate. A stable isotope analog of the product peptide served as internal standard, and a novel inhibitor cocktail minimized dephosphorylation by other major serine/threonine phosphatases. The assay was used to determine CN activity in peripheral blood mononuclear cells (PBMCs) isolated from 20 CNI-treated kidney transplant patients and 9 healthy volunteers. RESULTS Linearity was observed from 0.16 to 2.5 μmol/L of product peptide, with accuracy in the 15% tolerance range. Intraassay and interassay recoveries were 100.6 (9.6) and 100 (7.5), respectively. Michaelis–Menten kinetics for purified CN were Km = 10.7 (1.6) μmol/L, Vmax = 2.8 (0.3) μmol/min · mg, and for Jurkat lysate, Km = 182.2 (118.0) μmol/L, Vmax = 0.013 (0.006) μmol/min · mg. PBMC CN activity was successfully measured in a single tube with an inhibitor cocktail. CONCLUSIONS Because LC-MRM-MS is commonly used in routine clinical dosage of drugs, this CN activity assay could be applied, with parallel blood drug concentration monitoring, to a large panel of patients to reevaluate the validity of PBMC CN activity monitoring.

Simultaneous quantification of atorvastatin and active metabolites in human plasma by liquid chromatography–tandem mass spectrometry using rosuvastatin as internal standard

2006 ◽  
Vol 20 (9) ◽  
pp. 924-936 ◽  
Author(s):  
Ramakrishna V. S. Nirogi ◽  
Vishwottam N. Kandikere ◽  
Manoj Shukla ◽  
Koteshwara Mudigonda ◽  
Santosh Maurya ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Human Plasma ◽  
Internal Standard ◽  
Tandem Mass ◽  
Active Metabolites ◽  
Simultaneous Quantification ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

Development of a Nanoscale Liquid Chromatography/Electrospray Mass Spectrometry Methodology for the Detection and Identification of DNA Adducts

1997 ◽  
Vol 69 (16) ◽  
pp. 3161-3168 ◽  
Author(s):  
K. Vanhoutte ◽  
W. Van Dongen ◽  
I. Hoes ◽  
F. Lemière ◽  
E. L. Esmans ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Dna Adducts ◽  
Electrospray Mass Spectrometry ◽  
Detection And Identification
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