IntroductionDirect oral anticoagulants (DOACs) have been widely used in patients with thromboembolism. We previously reported that among DOACs, edoxaban (EDX), a factor Xa (FXa)-specific DOAC, most effectively inhibited the growth of syngeneic non-metastatic murine colon cancer cells implanted in mice via the protease-activated receptor 2 (PAR2) pathway. This study aimed to analyze the effects and mechanism of action of DOACs targeting thrombin or FXa on the metastasis of murine melanoma B16 cells implanted in mice.Materials and MethodsB16 cells (106cells in 100 μL) were implanted into the tail vein of 8-week-old female C57BL/6j mice (n = 5 per group), followed by daily oral administration of DOACs targeting thrombin (dabigatran etexilate [DABE], 50 mg/kg body weight [bw]) or FXa (rivaroxaban [RVX], 5 mg/kg bw; EDX, 10 mg/kg bw) for 14 days. The effects on tumor metastasis on day 15 and the inhibitory mechanism of the DOAC with the strongest inhibitory effect were analyzed.ResultsLung metastasis of B16 cells implanted in mice was significantly suppressed in the following order: EDX > RVX ≥ DABE, compared with the saline-treated group. DOPA (3,4-dihydroxyphenylalanine)-positive cell density was significantly reduced from approximately 1,250 cells/mm2in the saline group to approximately 600 cells/mm2(RVX and DABE) and approximately 400 cells/mm2(EDX;p < 0.05 or 0.01). Investigating the inhibitory mechanism of EDX revealed that inflammation-associated factors such as PAR2, interleukin 6 (IL-6), and transforming growth factor β1 (TGFβ1); angiogenic factors such as vascular endothelial growth factor A and angiopoietin-2; and epithelial–mesenchymal transition (EMT)-associated factors such as vimentin and snail, which were increased in the lungs of the saline-treated group, all significantly decreased in the EDX-treated group (p < 0.05 or 0.01). In contrast, intercellular tight junction factors exhibited an opposite trend. EDX also inhibited FXa-dependent production of melanin, IL-6, and TGFβ1 in in vitro cultured B16 cells.ConclusionAmong the tested DOACs, EDX showed the strongest inhibition of B16 cell metastasis in mice, likely via the suppression of inflammation, angiogenesis, and EMT mediated by the FXa-dependent PAR2 and TGFβ pathways in tumor and surrounding tissue cells.

Global warming and the developed worldwide awareness have persuaded efforts to minimize the generated hazardous wastes. As a result, “green” chemical procedures are being gradually included in science for sustainable development. This concept has been extended and inspired chemists to fabricate novel green carbon dots (CDs) from natural plants. Herein, we represent novel CDs synthesized by recycling seeds obtained from bell pepper as fluorescent probe for the determination of Edoxaban tosylate hydrate (EDO) a non-fluorescent drug; we exploit the advantage of the inner filter effect between the absorption peak of the drug and the emission peak of the CDs. This overlap resulted in quenching the fluorescence of CDs by increasing the concentration of EDO within the range 0.80–20.00 µg/mL with a limit of detection 0.23 and 0.22 µg/mL and a limit of quantitation 0.69 and 0.72 µg/mL for Microwave CDs and Plate CDs, respectively, at λex/λem 310/409 nm. Two facile preparation techniques for the CDs were used, the microwave-assisted method and the thermal decomposition method, using a single-step approach. The fabricated CDs were characterized using various techniques, including UV-vis, fluorescence and Fourier transform infrared spectroscopies, energy-dispersive X-ray, high-resolution transmission electron microscope, X-ray Diffaction, X-Ray photoelectron spectroscopy and zeta potential. The performance of the synthesized fluorescent probe for the determination of EDO was evaluated according to ICH guidelines. The accomplished results, together with the simplicity, sensitivity, and low cost of the developed probe, recommended its appropriateness for the routine quality control assay of EDO pharmaceutical formulation, as good % recovery was obtained upon the investigation of the marketed tablets with 99.77% and 98.79% recoveries for microwave CDs and plate CDs, respectively. The method’s greenness was evaluated using three integral matrices, the Blue Applicability Grade Index, the Complementary Green Analytical Procedure Index and Analytical Eco-Scale.Graphical abstract

The present invention relates to identified and prepared chiral impurities in Edoxaban Tosylate monohydrate (1). This work describes the synthesis of chiral impurities of each intermediate, including KSM and its drug substance and their characterization by spectral data (IR, MS,1H-NMR, and 13C-NMR). During the process development of Edoxaban Tosylate monohydrate (1) several unknown peaks were detected by high performance liquid column chromatography (HPLC) using chiral column. Edoxaban Tosylate monohydrate is the Tosylate salt form of edoxaban with binding one water molecule, an orally active inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Edoxaban having three chiral centers and has total of eight isomers, out of them only (SRS)-Edoxaban presents pharmacological activity being other seven are Edoxaban impurities. During the process development of edoxaban, the control of chiral impurities is challenging, and this is critical to remove from drug substance. Enantiomer of compound is led to form its starting material, and it tread on the heels of mechanism path up to final active pharmaceutical ingredients (API). This work helps to improve the efficacy and quality of the drug substance; therefore, concentration of these impurities must be controlled to the acceptable level.

Cancer-associated thromboembolism has been thoroughly investigated in previous studies, and direct oral anticoagulants (DOACs) were established for the treatment and prevention of venous thromboembolism (VTE). However, the risks of cancer-associated arterial thromboembolism (ATE) and the efficacy of DOACs remain unclear. To evaluate the risk factors and the clinical activity of edoxaban (EDO) for the prevention of ATE in patients with advanced lung cancer. From the prospective Rising-VTE/NEJ037 study which investigated VTE in newly diagnosed advanced lung cancer, we investigated the incidence rate and the risk factors of ATE as secondary endpoints. A total of 1008 patients were screened for VTE at study baseline and were followed up for 2 years. Excluding patients with a contraindication to DOACs, those with VTE were treated with EDO. ATE events were identified in 41 patients (4.1%). The most common location for ATE was cerebral infarction (N = 31, 75.6%), followed by myocardial infarction (N = 4, 9.8%). Multivariate analysis determined the incidence of VTE, D-dimer, a comorbidity of atrial fibrillation, and four other factors as independent risk factors of ATE. For VTE (+) patients, the incidence rate of ATE was 15.9% for the EDO administration (+) patients, compared with 11.1% for the EDO administration (-) patients (p = 0.626). The incidence rate of ATE was 4.1% over 2-year follow-up in advanced lung cancer patients. VTE was further identified as an independent risk factor for ATE, while intervention with DOACs was seen as less effective for the prevention of ATE in advanced lung cancer patients with VTE. This trial was registered in the Japan Registry of Clinical Trials (jRCTs061180025).

A 60-year-old male patient with metastasis from sigmoid colon cancer in the pancreatic uncinate process who received chemotherapy was treated with edoxaban (EDO) because of deep vein thrombosis. The pancreatic metastasis appeared to shrink, but the patient had repeated acute pancreatitis. An upper gastrointestinal endoscopy was performed to determine the cause. Bleeding from the major papilla and the minor papilla was detected, and he was diagnosed with hemosuccus pancreaticus. Pancreatic duct stenting was conducted from the minor papilla. The pancreatitis was then improved and the EDO dosage was reduced. The pancreatic duct stent fell off during the course. Hemosuccus pancreaticus has not relapsed after 1 year from the dropout of the stent. EDO was considered responsible for hemosuccus pancreaticus.

This study reveals one-step green synthesis of plant inspired silver nanoparticles (Ag-NPs). The synthesis procedure relies on the bio-reduction of Ag+ to Ag0 using orange waste (orange peel) extract as cheap, readily available, sustainable, biocompatible feedstocks as a reducing and stabilizing agent. The prepared Ag-NPs passed through a full characterization procedure for better confirmation and elucidation of optical and structural properties. The fluorescence of the prepared Ag-NPs has a quantum yield of 17.15% enabling its potential use in chemical sensing of drugs. Ag-NPs are conceived to be used as a fluorescent nano sensor for sensitive, ecofriendly, rapid spectrofluorimetric determination of two recent direct oral anticoagulants, namely, rivaroxaban (RIV) and edoxaban tosylate monohydrate (EDT); COVID-19 adjunctive drugs in their raw materials and pharmaceutical tablets. The fluorescence of the prepared Ag-NPs at 333 nm (λex=258nm)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${(\\uplambda }_{\ ext{ex}}=258 \ ext{nm})$$\\end{document} was found to be substantially quenched in existence of increasing concentrations of each drug. The quenching mechanisms were studied and explained. The validation of the method revealed linear correlation over the ranges of 0.5–10 µg/ml with an excellent regression correlation (r = 0.9999) for both drugs with minimum detection limits of 0.14 and 0.16 µg/ml for rivaroxaban and edoxaban tosylate monohydrate, correspondingly. Three different metrics were employed for verifying the greenness profile of the presented study. The findings of the greenness assessment were congruent and compatible with the green synthesis procedure, ecofriendly analysis, and the exclusion of using organic solvents and noxious materials opening an avenue for green synthesis of nanoparticles instead of chemical and physical methods.

Arg-Specific serine Protease-Targeted edoxaban tosylate monohydrate-Poly (lactic-co-glycolic acid) Nanoparticles: Investigating Stuart-Prower factor targeting and intestinal distribution through Ex-Vivo fluorescent visualization

The present research looked for ways to develop shielded nanoparticles (NPs)-drug transporters made of chitosan (CS) to enhance the bioavailability of edoxaban tosylate monohydrate (ETM) for oral administration by examining the correlation among design aspects and data from experiments using response surface methodology (RSM). ETM-loaded CS nanoparticles (ETM-CS-NPs) were developed using the ionic gelation of CS with tripolyphosphate (TPP). Utilising Zeta-sizer and scanning electron microscopy, the ETM-CS-NPs were evaluated for particle size (PS), zeta potential (ZP), surface morphology, polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Drug and polymer interactions in NPs were assessed using Fourier transform infra-red spectroscopy. The response surface approach and Design-Expert software optimised the ETM-CS-NPs. Using RSM, the effects of independent variables such as the amount of CS, the amount of TPP, and the amount of glacial acetic acid on PS, PDI and ZP were analysed. The optimal combination of PS (354.8 nm), PDI (0.509), ZP (43.7 + mV), % EE (70.3 ± 1.3) and % DL (9.1 ± 0.4) has been identified for the optimised ETM-CS-NPs. ETM-CS-NPs’ anticoagulant activity was evaluated using activated partial thromboplastin time (aPTT), prothrombin time (PT) and thrombin time (TT) assays. In conclusion, a practical and consistent method has been established, and its application has been proven in vitro, indicating its utility for future studies of the biological distribution of ETM-CS-NPs in vivo for specific antithrombotic treatments.

ABSTRACT Anticoagulant drugs currently play a crucial role in preventing severe deep vein thrombosis, heart attacks, heart valve diseases and contribute to the regulation of blood flow. Thus, the existing study reports the redox behaviour of Edoxaban (EDX) anticoagulant drug at bare glassy carbon electrode (GCE) for establishing sensitive, and selective adsorptive square wave – cathodic stripping voltammtric (Ads SW-CSV) probe for EDX detection. Under the optimal analytical parameters, the probe displayed good linear dynamic range (LDR) of EDX from 1.0 × 10−6 − 1.0 × 10−5 M. The probe displayed probe sensitivity, limits of detection (LOD) and quantification (LOQ) of 18.5 µA µM−1 cm−2, 3.3 × 10−7 and 1.0 × 10−6 M, respectively. The probe offered quick response, good anti-interference ability towards multiple co-existing species, good recovery (99.21 ± 5.02), reproducibility, and repeatability with relative standard deviation (RSD) of ± 3.0% at 1.0 × 10−6 M of EDX (n = 3). Intraday and interday precisions of the probe were 99.8 ± 1.74 and 99.54 ± 2.08% at 1.0 × 10−6 M of EDX, respectively. The probe was fruitfully applied for EDX detection in its formulations and its residue in water samples with good recovery (99.76 ± 3.768–101.43 ± 0.09) and precision (RSD < 3%) at low and high EDX levels. The tabulated Student t test (t tab =2.78) was higher than the experimental t exp = 1.3–1.7 at 95% probability (n = 5). The probe exhibited good sensitivity and selectivity towards EDX detection in drug formulation and environmental water samples. The probe has long-term stability and high level of anti-interference performance towards EDX detection.

Electrochemical oxidation of edoxaban and its determination in pharmaceutical samples and human serum

Reverse-phase high-performance liquid chromatography method has been developed for the determination of EDO-S1 stereoisomeric impurities such as isomer 1, isomer 2, isomer 3, isomer 4, isomer 5, isomer 6 and isomer 7 with good resolution using the column, Bakerbond C18 (150 × 4.6 mm; 3 μm). The separation was achieved with mobile phase-A (10 mM dipotassium hydrogen phosphate pH-7.0 with 10% orthophosphoric acid solution in Milli-Q water) and mobile phase-B (n-Propanol: Acetonitrile ratio of 20:30 % V/V), which consisted of mobile phase mixture in the combination of moilephase-A: mobile phase-B (85:15). The total run time was 30 min at 0.8 mL/min flow rate, 20 µL injection volume and 30 ℃ column oven temperature. The column eluate was monitored at 210 nm to quantify the impurities The method showed adequate specificity, sensitivity, linearity, accuracy, precision, and robustness inline to ICH tripartite guidelines. The limit of detection and quantification limits were 0.1 and 0.3 μg mL−1, respectively, for all isomeric impurities and EDO-S1. The developed method was found to be linear over the concentration range of LOQ to 150% of specification range for isomeric impurities with a correlation coefficient &gt;0.999. The method was precise (%RSD &lt; 5.0), robust, and accurate (with 85%–115% recovery).

Edoxaban tosylate monohydrate (EDTM) is present in class IV of the biopharmaceutics classification system (BCS), as it is poorly soluble and poorly permeable, which limits its bioavailability. The rationale of this study was to improve the permeability and solubility of EDTM by incorporating it into a self-micro-emulsifying drug delivery system (SMEDDS). Suitable excipients were selected and evaluated for their compatibility. The solubility of EDTM was evaluated for all excipients (oil, surfactant, and co-surfactants) at different ratios. Olive oil, Kolliphor RH40, and PEG-400 were chosen as the oil, surfactant, and co-surfactants, respectively, and were developed into a SMEDDS by adding 15 mg of EDTM. The optimized EDTM-SMEDDS (F1, F2, F3, and F4) were characterized for particle size, polydispersity index (PDI), zeta potential, stability, in vitro release, and ex vivo permeation studies. F2 showed a particle size of 56.43 ± 1.78, PDI of 0.190 and -3.30 ± 0.56 mV of zeta-potential. The enhanced release and permeability of F2 were observed for all other EDTM-SMEDDSs and raw EDTM dispersions. Upon storage under continuous temperature and accelerated stability conditions, F2 showed no signs of phase separation and was visually clear while retaining the %encapsulation efficiency and drug loading, that is, it was stable. The liquid EDTM-SMEDDS improved the bioavailability of EDTM.

This case report aims to present the diagnosis and treatment process of portal vein thrombosis, which occurred one week after laparoscopic appendectomy and required small bowel resection. A thirty-eight-year-old man was admitted with abdominal pain in the periumbilical and epigastric regions. He had a history of appendectomy and occlusive cerebrovascular disease. In the physical examination of the abdomen, tenderness was detected in the epigastric region on deep palpation. Leucocytosis, increased levels of alanine transaminase level, aspartate transaminase, gamma-glutamyl transferase, lactate dehydrogenase, c-reactive protein, and d-dimer were detected in laboratory analyses. CT scan revealed total thrombus in the portal vein, oedema in the segment of approximately 10 cm in the distal ileum, and free fluid in the pelvic region. Enoxaparin sodium was started. During follow-up, widespread defence and rebound in all quadrants of the abdomen occurred. 20 cm ileal resection with end ileostomy was performed. Enoxaparin sodium treatment was continued. On the 6th day of the service follow-up, the patient had left leg pain, and a subacute thrombus was detected in the main femoral, superficial femoral and deep femoral veins on doppler USG. Edoxaban tosylate 60 mg tablet every 24 hours started as an anti-coagulant treatment, and the patient was discharged without complications on the 18th day of hospitalisation.

Investigation of the electrochemical properties of edoxaban using glassy carbon and boron-doped diamond electrodes and development of an eco-friendly and cost effective voltammetric method for its determination

Abstract Background/Introduction In the ENVISAGE-TAVI AF (Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation) trial, edoxaban (EDX) was noninferior to vitamin K antagonists (VKAs) for preventing most adverse clinical events but was associated with increased major bleeding (MB). Presence of EDX dose reduction criteria applied in the trial (DRC; body weight ≤60 kg, CrCL 15–50 mL/min, concomitant use of selected P-glycoprotein-inhibitors) indicates a more vulnerable patient phenotype. Purpose Compare clinical outcomes after TAVI for AF patients with and without DRC stratified by anticoagulation strategy and age. Methods ENVISAGE-TAVI AF (NCT02943785) was a multicentre, open-label, randomised, controlled trial comparing EDX vs VKA in patients with AF as the indication for oral anticoagulation (OAC) after successful TAVI. In this analysis, outcomes—which included net adverse clinical events (NACE; composite all-cause death, myocardial infarction, ischaemic stroke, systemic thromboembolic event, valve thrombosis, or MB), intracranial haemorrhage, ischaemic stroke, all-cause death, cardiovascular (CV) death, non-CV death, MB bleeding, fatal MB bleeding, and major gastrointestinal bleeding (MGIB) —were compared in patients with vs without DRC, further stratified by OAC use, and age (&amp;lt; or ≥80 years [y]). Results Patients meeting DRC (n=637) were older, more often female, and had lower baseline CrCL than those without (n=740). In addition, these patients had significantly higher rates of NACE (P=0.0375) and all-cause death (P=0.0136). There were no differences in MB or MGIB rates between patients with vs without DRC. EDX resulted in more MB (hazard ratio [95% CI], 1.6 [1.1–2.5] and MGIB (2.6 [1.2–5.8]) than VKA only in patients without DRC. In patients aged &amp;lt;80 y meeting DRC, rates of all-cause death (P=0.0366) and CV death (P=0.0042) were significantly higher than those without DRC. Among patients aged &amp;lt;80 y, there were no differences in rates of clinical outcomes between EDX and VKA regardless of the presence or absence of DRC; Figure 1). In patients aged ≥80 y, there were no differences in rates of all-cause death, MB, or MGIB in those with or without DRC; Figure 2). Additionally in this age group, there was no difference in MB between patients on EDX and VKA both with and without DRC. However, there was more MGIB with EDX when there were no DRC. In patients aged ≥80 y with DRC, all-cause death was lower with EDX. Conclusions In this subanalysis of ENVISAGE-TAVI AF, the presence of DRC indicates a more vulnerable patient phenotype at higher risk for all-cause death after TAVI and in whom a lower EDX dose may have substantial benefits in terms of outcomes, including bleeding events, particularly in patients ≥80 y.Figure 1Figure 2

Introduction: The ENVISAGE-TAVI AF (NCT02943785) trial compared edoxaban (EDO) vs vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) after successful transcatheter aortic valve replacement (TAVR). The effect of baseline creatinine clearance (CrCl) on efficacy and safety of EDO vs VKA in these patients is not well understood. Hypothesis: The efficacy and safety of EDO vs VKA in patients with AF undergoing TAVR will vary across the range of baseline CrCl. Methods: In this post-hoc analysis from the ENVISAGE-TAVI AF trial, we stratified patients by oral anticoagulation (OAC) strategy (EDO vs VKA) and CrCl (CrCl ≥90 mL/min, CrCl 60-89 mL/min, CrCl 45-59 mL/min, CrCl 30-44 mL/min, CrCl ≤29 mL/min). Results: Of 1426 patients included, 46.3% (n = 676) had CrCl from 60 to 89 mL/min. Patients with lower CrCl trended older in age than those with higher CrCl ( Table 1 ). The annualized event rates for all outcomes tended to increase with decreasing CrCl ( Table 2 ). Across the range of CrCl, patients receiving EDO vs VKA had higher rates of major bleeding and major gastrointestinal bleeding but lower rates of non-cardiovascular death. Major bleeding did not translate into increased all-cause death. Rates of intracranial hemorrhage were higher with EDO vs VKA in patients with CrCl ≥90 mL/min but lower in all other patients. For all-cause death, differences between EDO and VKA were numerical and did not reach statistical significance. Conclusions: In this ENVISAGE-TAVI AF subanalysis, decrements of CrCl appeared to correlate with rates of adverse outcome parameters more than OAC strategy. Due to low event rates in some outcomes, these results should be interpreted with caution.

Edoxaban is an anti-coagulant medication and a director factor Xa inhibitor. A novel reverse phase liquid chromatography-mass spectrometry compatible method developed for separation and identification of new oxidative degradation impurities in edoxaban tosylate hydrate drug substance. The separation of three oxidative degradation impurities was achieved by using YMC Triart phenyl (250 × 4.6) mm, 5 µm column with mobile phase containing gradient elution of mobile phase-A as 10 mM ammonium acetate and mobile phase-B as acetonitrile:methanol (1:1)% (v/v). The flow rate of the mobile phase is 0.7 mL/min with a column temperature of 40 °C and detection wavelength of 290 nm. Edoxaban tosylate hydrate shows significant degradation in oxidative stress conditions and forms three oxidative degradation products. The degradation products were identified and characterized by using a high-resolution mass spectrometry quadrupole-time of flight mass detector. The three oxidative degradation impurities of Edoxaban drug substance were well resolved with each other and along with Edoxaban drug substance peak. Among the three oxidative degradation impurities di-N-oxide impurity was the new oxidative degradation impurity identified for the first time and a novel reverse-phase high-performance liquid chromatography method was developed for separation of the three oxidative degradation impurities.

A precise, sensitive eco-friendly, simple, rapid, and derivative spectrofluorimetric method was developed to quantify edoxaban tosylate monohydrate in pure form and pharmaceutical dosage form. Sudden death due to pulmonary embolism as a consequence of coronavirus infection (covid-19) is an emerging problem. As a result, the world health organization introduced new guidelines to treat patients with COVID-19 with oral anticoagulants. Edoxaban tosylate monohydrate is an oral anticoagulant that doesn’t require hospitalization after dose adjustment. This spectrofluorimetric method relies on the derivatization by 9-fluorenyl methyl chloroformate at room temperature in borate buffer pH 9.0. After excitation at 265 nm, the product is highly fluorescent at 309 nm. Many experimental factors influencing the reaction's stability and development were thoroughly investigated and optimized. The method validation was evaluated by using ICH guidelines and showed high precision and accuracy with an average percent recovery of 101.46% ± 1.02. The linear range was 5.0–50.0 ng/mL with a correlation coefficient of 0.9999, the LOD was 1.5 ng/mL, and the LOQ was 4.5 ng/mL. The green assessment of the method was achieved utilizing the eco-scale and the Green Analytical Procedure Index. There was no significant difference between the results of the suggested method and those of the reported method according to Statistical analysis.

The importance of the binary mixtures of the novel oral anticoagulants (NOACs): apixaban (APX), edoxaban tosylate (EDX) and rivaroxaban (RIV) with the lipid-lowering statin, rosuvastatin calcium (ROS) is highly emerging to save lives of cardiovascular patients as these combinations are used in prophylaxis from stroke. A high-performance thin-layer chromatography (HPTLC) method was developed for the quantitative assay of these life-saving mixtures in tablets and human plasma. Two mobile phases were developed for the assay in bulk and tablets; the first one: toluene‒ethyl acetate‒methanol‒25% ammonia (3.5:4.5:2:0.2, V/V) (method I) used for the three mixtures, and the second one: methanol‒25% ammonia (9.95:0.05, V/V) (method II) used for EDX/ROS mixture only. For analysis in human plasma, APX was used as internal standard in RIV/ROS and EDX/ROS mixtures using methods I and II, respectively, while RIV was used as internal standard in APX/ROS mixture using method I; the methods were validated according to the Food and Drug Administration (FDA) regulation for analysis in biological fluids. The method selectivity was demonstrated by its ability to simultaneously analyze the drugs in the presence of dosage form excipients and in the presence of plasma interferences (analysis in biological fluid) at single wavelength (291 nm) by use of the internal standard.

Formulation and Evaluation of Immediate-Release Tablets of Edoxaban Tosylate