Determination of rivaroxaban in patient’s plasma samples by anti-Xa chromogenic test associated to High Performance Liquid Chromatography tandem Mass Spectrometry (HPLC-MS/MS)

Derogis, Priscilla Bento Matos Cruz; Sanches, Lívia Rentas; Aranda, Valdir Fernandes de; Colombini, Marjorie Paris; Mangueira, Cristóvão Luis Pitangueira; Katz, Marcelo; Faulhaber, Adriana C.L.; Mendes, Claudio Ernesto Albers; Ferreira, Carlos Eduardo dos Santos; França, Carolina Nunes; Guerra, João Carlos de Campos

doi:10.1371/journal.pone.0171272

Cited by 38 publications

(31 citation statements)

References 33 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sample processing was performed by protein precipitation with methanol, as described previously (17). Briefly, methanol (400 μL) containing deuterated internal standard (IS) (rivaroxaban-d4, 500 ng/mL) was added to 200 μL of deproteinated samples that were centrifuged at 1800 g for 10 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Diagnostic accuracy of thromboelastometry and its correlation with the HPLC-MS/MS quantification test

Aranda

Derogis

Sanches

et al. 2019

Braz J Med Biol Res

View full text Add to dashboard Cite

The aim of the study was to evaluate the diagnostic accuracy of thromboelastometry for assessing rivaroxaban concentrations. The accuracy of thromboelastometry was compared with the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method, which is the gold standard for drug plasma monitoring (the reference standard). Forty-six clinically stable patients were treated with 10, 15, or 20 mg of rivaroxaban once daily (OD group) or 15 mg twice a day (BID group) (no particular indication for treatment). Patient samples were collected 2 h after the use of the medication (peak) and 2 h before the next dose (trough). The rivaroxaban plasma concentrations were determined via HPLC-MS/MS, and thromboelastometry was performed using a ROTEM® delta analyzer. There were significant prolongations in clotting time (CT) for the 10, 15, and 20 mg of rivaroxaban treatments in the OD groups. In the 15 mg BID group, the responses at the peak and trough times were similar. At the peak times, there was a positive correlation between the plasma concentration of rivaroxaban and CT (Spearman correlation rho=0.788, P<0.001) and clot formation time (rho=0.784, P<0.001), and a negative correlation for alpha angle (rho=−0.771, P<0.001), amplitude after 5 min (rho=−0.763, P<0.001), and amplitude after 10 min (rho=−0.680, P<0.001). The CT presented higher specificity and sensitivity using the cut-off determined by the receiver characteristics curve. ROTEM has potential as screening tool to measure possible bleeding risk associated with rivaroxaban plasma levels.

show abstract

Section: Methodsmentioning

confidence: 99%

“…These limitations support the increasing interest in the development of HPLC-MS/MS methods. In a previous work, we showed the ability of HPLC-MS/MS to quantify plasma rivaroxaban levels (17).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic accuracy of thromboelastometry and its correlation with the HPLC-MS/MS quantification test

Aranda

Derogis

Sanches

et al. 2019

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…Plasma concentration of RIV, CBZ, and PHT was determined by validated methods using high-performance liquid chromatography (1200 series HPLC; Agilent, Santa Clara, CA, USA) coupled with tandem mass spectrometry (Qtrap 4000; Sciex, Framingham, MA, USA) [32][33][34]. Chromatographic separation of analytes was conducted using a GEMINI-NX C18 column (50 mm × 2 mm; 5 µm; Phenomenex, Torrance, CA, USA) with a gradient elution of mobile phase, which contains 0.1% formic acid solution (A) and methanol (B) at a flow rate of 0.3 mL/min.…”

Section: Plasma Concentration and Pt Measurement Methodsmentioning

confidence: 99%

Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban

et al. 2020

View full text Add to dashboard Cite

Rivaroxaban (RIV) is commonly prescribed with carbamazepine or phenytoin (CBZ/PHT) in post-stroke seizure or post-stroke epilepsy patients. Although adverse events have been reported in several previous studies when they are coadministered, there are no studies of the interactions between these drugs. Therefore, our study was conducted to solve this lack of information. The potential effects of CBZ/PHT were investigated by comparing the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of RIV between the control group (RIV alone) and the test groups (RIV administered with CBZ/PHT) in rats using the noncompartmental analysis (NCA) and the compartmental model approach. The NCA results indicate that AUCt of RIV decreased by 57.9% or 89.7% and Cmax of RIV decreased by 43.3% or 70.0% after administration of CBZ/PHT, respectively. In addition, both CBZ and PHT generally reduced the effects of RIV on the prothrombin times of the blood samples. PK profiles of RIV were most properly described by a two-compartment disposition model with a mixed first- and zero-order absorption kinetics and a first-order elimination kinetics. The compartmental model approach showed that a 211% or 1030% increase in CL/F of RIV and a 33.9% or 43.4% increase in D2 of RIV were observed in the test groups by the effects of CBZ/PHT, respectively. In conclusion, CBZ and PHT significantly reduced RIV exposure and therefore reduced the therapeutic effects of RIV. Consequently, this might result in adverse events due to insufficient RIV concentration to attain its therapeutic effects. Further studies are needed to validate this finding.

show abstract

“…An electrospray ionization (ESI) source operated in positive ion mode was applied in the mass spectrometer. Multiple reaction monitoring (MRM) of the analyte (m/z 436.1→144.9) and internal standard (m/z 407.1→99.1) were used for the making of calibration curve 11,12 .…”

Section: Methodsmentioning

confidence: 99%

Untitled

2019

IJPSR

View full text Add to dashboard Cite

Rivaroxaban is utilized as a direct factor Xa inhibitor for the prevention and remedy of thromboembolic disorders. This study aimed to evaluate a generic version of rivaroxaban 10 mg tablet. Considering previous reports of safety and tolerability of a single dose (1.25-80 mg) of rivaroxaban, this study used a randomized, single-dose two-way crossover of rivaroxaban in 28 healthy volunteers, with a washout period of seven days. Analyses of blood samples were performed by a validated ultra-high performance liquid chromatography coupled with tandem mass spectrometry. An YMC-Pack ODS-AQ reversed-phase column with the mobile phase of acetonitrile and 10 mM ammonium acetate pH = 3 (70:30, v/v) at a flow rate of 0.3 mL.min-1 under isocratic elution was selected for the analysis. A range of 2.5-600 ng.mL-1 was obtained for the calibration curve. Pharmacokinetic parameters were calculated for the bioequivalence assessment. The results showed that two formulations have similar pharmacokinetics. The 90% confidence interval of the mean ratios of the test versus reference formulation of Ln transformed AUC 0-30 (82.0-98.0), AUC 0-inf (81.3-105.2), and C max (82.4-104.4) were within the acceptable range of 80-125%.

show abstract

Determination of rivaroxaban in patient’s plasma samples by anti-Xa chromogenic test associated to High Performance Liquid Chromatography tandem Mass Spectrometry (HPLC-MS/MS)

Cited by 38 publications

References 33 publications

Diagnostic accuracy of thromboelastometry and its correlation with the HPLC-MS/MS quantification test

Diagnostic accuracy of thromboelastometry and its correlation with the HPLC-MS/MS quantification test

Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban

Untitled

Contact Info

Product

Resources

About