Background: Apixaban's technical sheet does not recommend its use in clinical practice for patients with chronic kidney disease undergoing haemodialysis. However, recent studies indicate that apixaban could be a safe oral anticoagulant in these kinds of patients who do not present valvular atrial fibrillation. We developed and validated ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) procedures for measuring apixaban concentrations in plasma, dialysate liquid, and urine.
Material and methods: Simple protein precipitation was implemented to prepare samples. Chromatographic separations were achieved on an Acquity®-UPLC®-BEHTM (2.1x100 mm id, 1.7 µm) reverse-phase C18 column using a water/acetonitrile non-linear gradient containing 0.1 % formic acid at a 0.4 mL/min flow rate. Apixaban and its internal standard (apixaban-d3) were detected by electrospray ionisation mass spectrometry in positive and multiple reaction monitoring modes, using transitions of 460.3 → 199.0/443.2 and 463.3 → 202.0, respectively.
Results: No significant interferences and carry-overs were observed. Precisions, absolute relative biases, normalised-matrix factors, and normalised recoveries were ≤ 12.2%, ≤8.0%, 94.3-105.1%, and 93.9-105.4%, respectively. Linearity was observed between 5 and 500 μg/L for plasma/dialysate liquid and 5-1000 μg/L for urine.
Conclusions: The validated UHPLC-MS/MS procedures could help support a pharmacokinetic study in non-valvular atrial fibrillation subjects with chronic kidney disease undergoing haemodialysis and apixaban-based anticoagulant therapy.
Keywords: Apixaban; Dialysate liquid; Plasma; UHPLC-MS/MS; Urine.
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