Determination of rivaroxaban – a novel, oral, direct Factor Xa inhibitor – in human plasma by high-performance liquid chromatography–tandem mass spectrometry

Rohde, G.

doi:10.1016/j.jchromb.2008.07.015

Cited by 125 publications

(109 citation statements)

References 14 publications

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“…Laboratory site D measured rivaroxaban levels using tandem high-performance liquid chromatography/mass spectrophotometry (LC-MS/MS) as previously described. 14 All anti-Xa assays were performed using rivaroxaban calibrators. For each anti-Xa kit studied, a single source (Biophen) rivaroxaban calibrator was used, consisting of 3 levels with drug concentrations from 0 to approximately 500 ng/mL.…”

Section: Methodsmentioning

confidence: 99%

Comparison of Anti-Xa and Dilute Russell Viper Venom Time Assays in Quantifying Drug Levels in Patients on Therapeutic Doses of Rivaroxaban

Gosselin

Funk

Taylor

et al. 2014

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Rivaroxaban is a new oral anticoagulant that functions as a direct anti-Xa inhibitor. Although routine monitoring is not required, measurement of plasma concentrations may be necessary in certain clinical situations. Routine coagulation assays, such as the prothrombin time and, to a lesser degree, activated partial thromboplastin time, correlate with drug concentration, but because of reagent variability, these methods are not reliable for determining rivaroxaban anticoagulation.Objective.-To compare different methods and calibrators for measuring rivaroxaban, including the chromogenic anti-Xa assay, which, when calibrated with a rivaroxaban standard, may be more appropriate for determining anticoagulation.Design.-We compared measured rivaroxaban concentrations with the same anti-Xa kit but used different calibrators, with different anti-Xa kits but the same calibrators, with antithrombin-supplemented anti-Xa kit versus nonsupplemented kits, and with 2 methods based on rivaroxaban-calibrated, high-phospholipid, dilute Russell viper venom time. Regression and paired t test statistics were used to determine correlation and significant differences among methods and calibrator sources.Results.-Although there was strong correlation, statistically significant biases existed among methods that report rivaroxaban levels. A single-source calibrator did not alleviate those differences among methods. High-phospholipid Russell viper venom reagents correlated with rivaroxaban concentration but were not better than chromogenic anti-Xa methods.Conclusions.-Rivaroxaban-calibrated, anti-Xa measurements correlate well, but the clinical significance of the variation with rivaroxaban measurements is uncertain. The antithrombin-supplemented, anti-Xa method should be avoided for measuring rivaroxaban.

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Section: Methodsmentioning

confidence: 99%

Comparison of Anti-Xa and Dilute Russell Viper Venom Time Assays in Quantifying Drug Levels in Patients on Therapeutic Doses of Rivaroxaban

Gosselin

Funk

Taylor

et al. 2014

Archives of Pathology &Amp; Laboratory Medicine

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“…Samples were analyzed for rivaroxaban concentration at time 0 (control), 0.5, 1, 2, and 4 hours using a validated HPLC coupled to tandem mass spectrometry (liquid chromatography-mass spectrometry [LC-MS/MS]) method. 13 NG tube compatibility (extent of degradation or adsorption of rivaroxaban from a suspension onto the inner surface of an NG tube) was assessed for polyvinyl chloride (PVC; Argyle TM Salem Sump TM Tube; Covidien; Mansfield, MA) and silicone (Argyle TM Silicone Salem Sump TM tube; Tyco) tubes. A 20 mg rivaroxaban tablet was crushed to a fine powder, and triplicate samples were suspended in 50 mL of water.…”

Section: In Vitro Assessmentmentioning

confidence: 99%

Rivaroxaban crushed tablet suspension characteristics and relative bioavailability in healthy adults when administered orally or via nasogastric tube

Moore

Krook

Vaidyanathan

et al. 2014

Clinical Pharm in Drug Dev

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Purpose: Because some patients have difficulty swallowing a whole tablet, we investigated the relative bioavailability of a crushed 20 mg rivaroxaban tablet and of 2 alternative crushed tablet dosing strategies. Methods: Stability and nasogastric (NG) tube adsorption characteristics of a crushed rivaroxaban tablet were assessed. Then, in 55 healthy adults, relative bioavailability of rivaroxaban administered orally as a whole tablet (Reference [WholeOral]), crushed tablet in applesauce suspension (Crushed-Oral), or crushed tablet in water suspension via NG tube (Crushed-NG) were determined. Results: There were no significant changes in mean percent of non-degraded rivaroxaban recovered over 4 hours from crushed tablet suspensions (>98.4% recovery across all suspensions and time points) or after NG tube exposure (recovery: 99.1% for silicone and 98.9% for polyvinyl chloride NG tubes). Relative bioavailability was similar between Crushed-Oral and Reference dosing (C max and AUC 1 were within the 80-125% bioequivalence limits). Relative bioavailability was also similar between the Crushed-NG and Reference dosing (AUC 1 was within bioequivalence limits; C max [90% CI range: 78.5-85.8%] was only slightly below the 80% lower bioequivalence limit). Conclusions: A crushed rivaroxaban tablet was stable and when administered orally or via NG tube, displayed similar relative bioavailability compared to a whole tablet administered orally.Keywords rivaroxaban, factor Xa inhibitor, nasogastric tube, bioavailability, pharmacokinetics Rivaroxaban is a novel oral anticoagulant that selectively inhibits factor Xa (FXa) at the beginning of the final common pathway of the coagulation cascade; thus, blocking the downstream burst of thrombin generation. [1][2][3][4] Rivaroxaban is readily absorbed after oral tablet administration, with maximum plasma concentrations (C max ) occurring approximately 2-4 hours after dosing. 5,6The 20 mg tablet displays an absolute bioavailability of approximately 66% in a fasted state, increasing by approximately 39% when administered with food.7 A similar absorption profile and food effect may be expected for the 15 mg tablet. Therefore, both dose strengths should be administered with food. Both doses are approved for DVT or PE treatment, reducing the risk of DVT and PE recurrence and for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. 8 The 10 mg dose is approved for DVT prophylaxis in patients undergoing hip or knee replacement surgery and has near complete absorption (80-100% absolute bioavailability) that is not affected by food.9 The half-life of rivaroxaban ranges from 5 to 13 hours in healthy subjects. 8 Dysphagia (difficulty swallowing food or liquids) is associated with many health conditions and complications may include aspiration pneumonia, dehydration, or malnutrition. In the United States, dysphagia is estimated to affect more than 18 million adults. More than 40% of

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“…The RIV was approved for marketing by Health Canada and European Commission in 2008. In the literature, there is an HPLC-MS method for the determination of RIV in human plasma for pharmacokinetic studies (Rohde, 2008). However, there is no method reported for the quantification of RIV in pharmaceutical dosage forms.…”

Section: Introductionmentioning

confidence: 99%

RP-HPLC method development and validation for estimation of rivaroxaban in pharmaceutical dosage forms

Çelebi̇er¹,

Reçber²,

Koçak³

et al. 2013

Braz. J. Pharm. Sci.

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Rivaroxaban, an anti-clotting medication, acts at a crucial point in the blood-clotting process and stops the formation of blood clots. In this study, RP-HPLC method was developed for the determination of rivaroxaban in tablets (Xarelto ® (10 mg)). Phenomenex Luna 5 µm C18 100 Å LC Column (250 x 4.6 mm) was used at 40 o C. Isocratic elution was performed with ACN:Water (55:45 v/v) mixture. The flow rate was 1.2 mL min -1 and UV detection was at 249 nm. Internal standard (Caffeine) and rivaroxaban were eluted within 2.21 and 3.37 minutes, respectively. The developed method was validated according to the ICH guidelines and found to be linear within the range 0.005 -40.0 µg mL -1 . The method was accurate, precise, robust and rapid. Thus, it was applied successfully for the quality control assay of rivaroxaban in tablet dosage form.Uniterms: HPLC. Rivaroxaban. Validation. System suitability. Stability-indicating. Pharmaceutical dosage form.Rivaroxabana, fármaco anticoagulante, atua em um ponto crucial no processo de coagulação do sangue e impede a formação de coágulos sanguíneos. Neste estudo, desenvolveu-se método de RP-HPLC para a determinação de rivaroxabana em comprimidos (Xarelto ® (10 mg)). Utilizou-se coluna LC (250 x 4,6 mm) Phenomenex Luna C18 5 mm 100 Å a 40 o C. Realizou-se eluição isocrática com ACN: água (55:45 v/v). O fluxo foi de 1,2 mL min-1 e a detecção de UV foi a 249 nm. Padrão interno (cafeína) e rivaroxabana eluíram em 2,21 e 3,37 minutos, respectivamente. O método desenvolvido foi validado de acordo com as diretrizes do ICH e mostrou-se linear na faixa 0,005-40,0 mg mL -1 . O método foi exato, preciso, robusto e rápido. Assim, foi aplicado com êxito para o ensaio de controle de qualidade da Rivaroxabana na forma de comprimidos.Unitermos: HPLC. Rivaroxabana. Validação. Adequação do sistema. Indicador de estabilidade. Forma farmacêutica.

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Determination of rivaroxaban – a novel, oral, direct Factor Xa inhibitor – in human plasma by high-performance liquid chromatography–tandem mass spectrometry

Cited by 125 publications

References 14 publications

Comparison of Anti-Xa and Dilute Russell Viper Venom Time Assays in Quantifying Drug Levels in Patients on Therapeutic Doses of Rivaroxaban

Comparison of Anti-Xa and Dilute Russell Viper Venom Time Assays in Quantifying Drug Levels in Patients on Therapeutic Doses of Rivaroxaban

Rivaroxaban crushed tablet suspension characteristics and relative bioavailability in healthy adults when administered orally or via nasogastric tube

RP-HPLC method development and validation for estimation of rivaroxaban in pharmaceutical dosage forms

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