Determination of free and total warfarin concentrations in plasma using <scp>UPLC MS</scp>/<scp>MS</scp> and its application to a patient samples

Radwan, Mahasen A.; Bawazeer, Ghada; Aloudah, Nouf M.; AlQuadeib, Bushra T.; Aboul‐Enein, Hassan Y.

doi:10.1002/bmc.1616

Cited by 33 publications

(22 citation statements)

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“…Although a 100 μ L [6, 7] or 1 mL aliquot of plasma [8] was used, such an analytical method was questionable due to low specificity and sensitivity of UV detection. Therefore, several methods of HPLC with mass spectrometry (MS) and HPLC with tandem mass spectrometry (MS/MS) have been developed for warfarin quantification in single-reaction monitoring mode [5, 9, 10] or multiple-reaction monitoring mode [4, 11–13]. Warfarin has been isolated by solid-phase extraction [9, 12], liquid/liquid extraction [4, 5, 10, 13], or simple protein precipitation with ZnSO 4 [11].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, several methods of HPLC with mass spectrometry (MS) and HPLC with tandem mass spectrometry (MS/MS) have been developed for warfarin quantification in single-reaction monitoring mode [5, 9, 10] or multiple-reaction monitoring mode [4, 11–13]. Warfarin has been isolated by solid-phase extraction [9, 12], liquid/liquid extraction [4, 5, 10, 13], or simple protein precipitation with ZnSO 4 [11]. Nevertheless, the volume of plasma required for one analysis has been rather high: 50 μ L [10], 200 μ L [4, 12, 13], 300 μ L [9], or even 1 mL [4].…”

Section: Introductionmentioning

confidence: 99%

“…Warfarin has been isolated by solid-phase extraction [9, 12], liquid/liquid extraction [4, 5, 10, 13], or simple protein precipitation with ZnSO 4 [11]. Nevertheless, the volume of plasma required for one analysis has been rather high: 50 μ L [10], 200 μ L [4, 12, 13], 300 μ L [9], or even 1 mL [4]. At the same time, in such studies, blood and plasma samples are usually collected from small animals like mice and rats.…”

Section: Introductionmentioning

confidence: 99%

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Quantification of Warfarin in Dried Rat Plasma Spots by High-Performance Liquid Chromatography with Tandem Mass Spectrometry

Chernonosov

2016

Journal of Pharmaceutics

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This paper presents the development and validation of a novel method for quantification of the oral anticoagulant drug warfarin in dried plasma spots (DPS) by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Blood plasma was chosen as a biological fluid to preclude the influence of the hematocrit on the results of the analysis. A 30 μL sample of rat plasma was placed onto Whatman 903 Protein Saver Card and was allowed to dry. A single DPS is sufficient for preparing eight 3.2 mm discs, each containing approximately 1.5–1.6 μL of plasma. Warfarin extraction from one 3.2 mm disc was carried out by adding 200 μL of the acetonitrile : water mixture (1 : 1, v/v) containing 10 mM NH4COOH (pH 4.0), with incubation on a shaker at 1000 rpm for 1 h at 25°C. After chromatographic separation, warfarin and coumachlor (an internal standard) were measured using negative-ion multiple-reaction monitoring with ion transitions m/z 307 → 161 for warfarin and m/z 341 → 161 for the internal standard. The working range of this method is 10–10,000 ng/mL. Within this range, intra- and interday variability of precision and accuracy was <13% and recovery was 82–99%. The results indicate that the new method requires only small plasma samples and may be useful for pharmacokinetic research on warfarin.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantification of Warfarin in Dried Rat Plasma Spots by High-Performance Liquid Chromatography with Tandem Mass Spectrometry

Chernonosov

2016

Journal of Pharmaceutics

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“…It was administrated orally in the form of racemic mixture R-and S-WAR as treatment and prophylaxis of Venous Thromboembolism [1][2][3]. S-WAR is 3-5 times potent that Renantiomer, metabolised by P450 (CYP) 2C9 to form inactive S-7-hydroxy metabolite (7-OH-WAR) [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Although some of them used for chiral separation of warfarin and hydroxylated metabolites, they used non-specific detectors as UV and florescence [16][17][18]. Reported LC/MS methods for WAR were use either achiral separation or chiral separation with only limited consideration of metabolites [3,15,19]. The novelty of my method comes from it used for separation of enantiomers of WAR and three of its metabolites.…”

Section: Introductionmentioning

confidence: 99%

Enantiomeric separation and quantitation of warfarin and its metabolites in human plasma by LC-MS/MS

Mostafa

2016

Eur. J. Chem.

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The enantiomeric separation of warfarin (WAR) enantiomers and its hydroxy metabolites positional isomers is described in this work. The utilization of chiral chromatography coupled to Tandem mass spectrometry helps to achieve that. The developed method was able to separate R,S-warfarin and enantiomers of 4,7,10-hydroxy warfarin in human plasma. Plasma samples were processed with simple protein precipitation with acetonitrile. The chromatographic separation was done on chiral Astec Chirobiotic V column with gradient flow of 0.1% aqueous formic acid and 0.1% formic in acetonitrile:water (95:5, v:v). The mass spectroscopic detection was done via negative mode multiple reaction monitoring (MRM) on a triple quadrupole mass spectrometer coupled with positive electrospray ionization (ESI). Linearity of the method was valid over a concentration range of 125.00-0.13 µg/mL for racemic WAR, 47.000-0.088 µg/mL for racemic 4'-OH-WAR, 56.00-0.18 µg/mL for racemic 7-OH-WAR and 56.00-0.02 µg/mL for racemic 10-OH-WAR. The LLOQs were found to be 0.13 µg/mL for racemic WAR, 0.088 µg/mL for racemic 4'-OH-WAR, 0.18 µg/mL for racemic 7-OH-WAR and 0.02 µg/mL for racemic 10-OH-WAR. The method was validated for matrix effect, intra-and inter-day precision, freeze/thaw and storage stability. Accuracy and precision were within acceptable range (<15%). Enantiomeric forms of WAR and its metabolites were separated by the chiral column. Standards for R-and S-WAR identified peak 2 as S-WAR while metabolite peaks could not be definitively identified. Peak 2 for 7-OH-WAR gave higher blood levels, while the opposite applied to 10-OH-WAR. KEYWORDS

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Study on the interaction of plasma protein binding rate between edaravone and taurine in human plasma based on HPLC analysis coupled with ultrafiltration technique

Tang

et al. 2014

Biomedical Chromatography

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In this work, two high-performance liquid chromatography (HPLC) assays were developed and validated for the independent determination of edaravone and taurine using 3-methyl-1-p-tolyl-5-pyrazolone and L-glutamine as internal standards. In in vitro experiments, human plasma was separately spiked with a mixture of edaravone and taurine, edaravone or taurine alone. Plasma was precipitated with acetonitrile containing 0.1% formic acid. Ultrafiltration was employed to obtain the unbound ingredients of the two drugs. The factors that might influence the ultrafiltration effiency were elaborately optimized. Plasma supernatant and ultrafiltrate containing taurine were derivated with o-phthalaldehyde and ethanethiol in the presence of 40 mmol/L sodium borate buffer (pH 10.2) at room temperature within 1 min. Chromatographic separations were achieved on an InertSustain C18 column (250 × 4.6 mm, 5 µm). Isocratic 50 mmol/L ammonium acetate-acetonitrile and gradient 50 mmol/L sodium acetate (pH 5.3)-methanol were respectively selected as the mobile phase for the determination of edaravone and taurine. All of the validation data including linearity, extraction recovery, precision, accuracy and stability conformed to the requirements. Results showed that there were no significant alterations in the plasma protein binding rate of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible.

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Determination of free and total warfarin concentrations in plasma using UPLC MS/MS and its application to a patient samples

Cited by 33 publications

References 29 publications

Quantification of Warfarin in Dried Rat Plasma Spots by High-Performance Liquid Chromatography with Tandem Mass Spectrometry

Quantification of Warfarin in Dried Rat Plasma Spots by High-Performance Liquid Chromatography with Tandem Mass Spectrometry

Enantiomeric separation and quantitation of warfarin and its metabolites in human plasma by LC-MS/MS

Study on the interaction of plasma protein binding rate between edaravone and taurine in human plasma based on HPLC analysis coupled with ultrafiltration technique

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