As an anticoagulant, Edoxaban (EDX) is a high risk drug that may cause a life-threatening bleeding. Also, it is prescribed as a chronic therapy for atrial fibrillation and venous thromboembolism patients. They are special population that needs appropriate care and optimum dosing of EDX. Hence, its monitoring in the patient plasma is fundamental, especially in emergency and special circumstances. However, such patient mostly receives many drugs of different pharmacological classes, side by side with EDX. This study represents the first attempt to quantify EDX in plasma without interference of the plasma matrix or concomitant medications. An accurate RP-HPLC-DAD method was developed for this purpose. It succeeded to monitor EDX level, selectively, without interference of plasma matrix or 16 of its frequently co-administered drugs. All drugs were extracted from plasma samples by protein precipitation followed by evaporation and concentration. EDX was well resolved from the co-administered drugs on C8 column using linear gradient elution of methanol and phosphate buffer (pH 4), at a flow rate of 1 mL/min. EDX appeared at retention time 9.6 min and was quantified at its λmax (290 nm). It exhibited a linear response over the concentration range of 0.15-2.2 μg/mL plasma which covers the reported therapeutic concentration. The suggested method fulfilled the US FDA guidelines for bioanalytical method validation. The developed method is fully discussed in comparison with the reported techniques. An in vivo study was performed to ensure applicability of the method on real plasma samples without interference from plasma matrix, co-administered drugs or the expected metabolites. It presented a unique selectivity of the method that guarantees accurate laboratory monitoring of EDX in plasma in almost all combined treatments including such novel oral anticoagulant drug.
Keywords: Co-administered drugs; Edoxaban; HPLC-DAD; NOACs; Plasma; Protein precipitation.
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