Development, validation and application of a new HPLC-DAD method for simultaneous quantification of apixaban, dabigatran, edoxaban and rivaroxaban in human plasma

Gouveia, Filipa; Bicker, Joana; Santos, Joana Vieira dos; Rocha, Marília; Alves, Gilberto; Falcão, Amı́lcar; Fortuna, Ana

doi:10.1016/j.jpba.2020.113109

Cited by 51 publications

(25 citation statements)

References 18 publications

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“…Most published methods applied highly sensitive techniques, for example, LC–MS/MS, once low concentrations of this drug are found in plasma (ng/mL). Among the published methodologies for sample preparation, it is possible to observe that protein precipitation (Boehr & Haen, 2017; Derogis et al, 2017; Gai et al, 2019; Gouveia et al, 2020; Iqbal et al, 2015; Korostelev et al, 2014; Kuhn et al, 2015; Rohde, 2008; Shukla et al, 2020; Varga et al, 2017; Wiesen et al, 2017; Yadav & Dubey, 2017) is the most common one among other more costly and more complex techniques, such as SPE (Baldelli et al, 2016; Çelebier et al, 2016; Gouveia et al, 2020; Reddy et al, 2016; Shaikh et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

“…The expectation surrounding the expiry of the Xarelto patent stimulated the development of quantification assays based on LC–MS and UV–Vis (LC–UV) detector for pharmacokinetics, bioequivalence, and drug monitoring studies (Baldelli et al, 2016; Boehr & Haen, 2017; Çelebier et al, 2016; Derogis et al, 2017; Foerster et al, 2018; Gai et al, 2019; Gouveia et al, 2020; Iqbal et al, 2015; Korostelev et al, 2014; Kuhn et al, 2015; Reddy et al, 2016; Rohde, 2008; Shaikh et al, 2020; Shukla et al, 2020; Varga et al, 2017; Wiesen et al, 2017; Yadav & Dubey, 2017). Thus, the expected popularization that will accompany the introduction and availability of generic products will require fast and simple methods for drug monitoring, capable of enabling satisfactory therapeutic drug monitoring and toxicokinetic studies.…”

Section: Introductionmentioning

confidence: 99%

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Sensitive LC–MS/MS method for quantification of rivaroxaban in plasma: Application to pharmacokinetic studies

Oliveira

Davanço

Campos

et al. 2021

Biomedical Chromatography

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Rivaroxaban is an anticoagulant (orally active direct Xa inhibitor) considered to reduce the risk of stroke and systemic embolism and treat deep vein thrombosis, pulmonary embolism, and other cardiovascular complications. Bioanalytical methods for rivaroxaban quantification in plasma are necessary for application in pharmacokinetic studies, as well as in drug therapeutic monitoring. In this work, we developed and validated a sensitive bioanalytical method using LC–MS/MS for rivaroxaban quantification in human plasma using an one‐step liquid–liquid extraction. The linear concentration range was 1–600 ng/mL. The bioanalytical method was also applied to pharmacokinetic studies in healthy volunteers under fasting and fed conditions. The results demonstrated that the method is rapid, sensitive, and adequate for application in pharmacokinetic studies.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sensitive LC–MS/MS method for quantification of rivaroxaban in plasma: Application to pharmacokinetic studies

Oliveira

Davanço

Campos

et al. 2021

Biomedical Chromatography

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“…Based on the characteristics of PPN (a polar molecule with several chromophore groups, Figure 1) and the purpose of the analytical method (the quantification of an analyte in the biological matrix during the kinetic assay), reversed‐phase HPLC is the most obvious choice to obtain a selective method against skin contaminants with the rapid elution of the analyte (Gouveia et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

Development of a reversed‐phase high‐performance liquid chromatographic method for the determination of propranolol in different skin layers

Cunha-Filho

Rocha

Duarte

et al. 2020

Biomedical Chromatography

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The aim of this work was to develop and validate an analytical method using HPLC for the determination of propranolol in the different layers of the skin to be used in kinetic studies of skin permeation. The development of the method was based on the suitability of the chromatogram, and the validation followed the international health regulation for bioanalytical methods. In addition, the method was tested in an in vitro permeation assay using porcine skin. The drug was determined using an RP‐C18 column at 30°C, a mobile phase comprising acidic aqueous phase:acetonitrile (75:25 v/v), at a flow rate of 1.0 mL min−1, and UV detection at 290 nm. The method was demonstrated to be selective against skin contaminants, linear in a wide range of concentrations (3–20 μg mL−1), sensitive enough to quantify less than 0.1% of the drug dosage in skin matrices, and precise regardless of analysis variations such as day of analysis, analyst, or equipment. In addition, the method presented a high drug extraction capacity greater than 90% for all skin layers (stratum corneum, hair follicle, and remaining skin). Finally, the method was successfully tested in skin permeation assays, proving its value in the development of topical formulations containing propranolol.

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“…Of note, the destabilization of the HSA structure starts at 20% DMSO 20 . The DOACs concentration was determined spectrophotometrically 21,22 …”

Section: Methodsmentioning

confidence: 99%

Binding of direct oral anticoagulants to the FA1 site of human serum albumin

Pasquadibisceglie

Masi

et al. 2020

J of Molecular Recognition

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The anticoagulant therapy is widely used to prevent and treat thromboembolic events. Until the last decade, vitamin K antagonists were the only available oral anticoagulants; recently, direct oral anticoagulants (DOACs) have been developed. Since 55% to 95% of DOACs are bound to plasma proteins, the in silico docking and ligand‐binding properties of drugs apixaban, betrixaban, dabigatran, edoxaban, and rivaroxaban and of the prodrug dabigatran etexilate to human serum albumin (HSA), the most abundant plasma protein, have been investigated. DOACs bind to the fatty acid (FA) site 1 (FA1) of ligand‐free HSA, whereas they bind to the FA8 and FA9 sites of heme‐Fe(III)‐ and myristic acid‐bound HSA. DOACs binding to the FA1 site of ligand‐free HSA has been validated by competitive inhibition of heme‐Fe(III) recognition. Values of the dissociation equilibrium constant for DOACs binding to the FA1 site (ie, calcKDOAC) derived from in silico docking simulations (ranging between 1.2 × 10−8 M and 1.4 × 10−6 M) agree with those determined experimentally from competitive inhibition of heme‐Fe(III) binding (ie, expKDOAC; ranging between 2.5 × 10−7 M and 2.2 × 10−6 M). In addition, this study highlights the inequivalence of rivaroxaban binding to mammalian serum albumin. Given the HSA concentration in vivo (~7.5 × 10−4 M), values of KDOAC here determined indicate that the formation of the HSA:DOACs complexes in the absence and presence of FAs and heme‐Fe(III) may occur in vivo. Therefore, HSA appears to be an important determinant for DOACs transport.

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Development, validation and application of a new HPLC-DAD method for simultaneous quantification of apixaban, dabigatran, edoxaban and rivaroxaban in human plasma

Cited by 51 publications

References 18 publications

Sensitive LC–MS/MS method for quantification of rivaroxaban in plasma: Application to pharmacokinetic studies

Sensitive LC–MS/MS method for quantification of rivaroxaban in plasma: Application to pharmacokinetic studies

Development of a reversed‐phase high‐performance liquid chromatographic method for the determination of propranolol in different skin layers

Binding of direct oral anticoagulants to the FA1 site of human serum albumin

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