AIM:To develop an LC MS
method for the determination of
ranolazine concentration in dog
plasma and study
pharmacokinetics of ranolazine in Beagle dog. METHOD:20 μl plasma was mixed 10 min with 300 μl acetonitrile. After being centrifuged,10 μl supernatant was injected into a Shim pack C 18 150 mm×2 0 mm column. The mobile phase consisted of acetonitrile 0 05% acetic acid(60∶40, v/v ) at flow rate of 0 2 ml/min. The elute from the HPLC column was plumbed directly into APCI probe. Analysis in the mass spectrometer was operated in the selected ion monitoring model. The mass spectrometers was operated in SIM m/z 428 for ranolazine and 344 for DDPH (as internal standard). Dog blood samples were obtained after oral and intravenous administration of 25 mg/kg respectively.Ranolazine concentrations in plasma were determined and pharamcokinetic parameters were also estimated. RESULT:Recoveries of ranolazine at 0 16,0 62 and 10 0 μg/ml were 90 8,87 0 and 79 3% respectively. The standard curve was linear in the range of 0 039～10 00 μg/ml.The relative standard derivation of intra day and inter day was smaller than 10%.Terminal phase t 1/2 were estimated to be 7 31 and 5 67 hours after
ig and iv of 25 mg/kg ranolazine. Peak concentration(4 32± 1 25 μg/ml) occurred at 1 0±0 6 hours after ig. Absolute bioavailability was (72 6±15 6)% for ig. CONCLUSION:The bioanalytical method of LC MS is suitable for pharmacokinetic study of ranolazine. Oral absorption of ranolazine occurs rapidly and completely in dogs.
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