Abstract: AIM: The LC-MS/MS method was developed and validated,and assessed the pharmacokinetic properties after a single dose of 500, 1000, or 1500 mg of ranolazine in healthy Chinese volunteers.METHODS: Twelve Chinese subjects (6 men, 6 women) were enrolled in the single-dose phase of the PK study. The study were assigned to open-label, randomized-sequence, 3×3 latin square design which consisted of three 1-day treatment periods and two 7-day washout periods.Volunteers were randomly allocated to receive a single dose of 500, 1000, or 1500 mg of ranolazine (sustained-release tablets), sequential blood samples (4 mL each) were collected into heparin tubes at 0 hour (before administration) and 0.5, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0,and 48.0 hours after administration. The LC-MS/MS method was developed and validated.RESULTS:The main PK parameters for ranolazine after administration of a single oral dose of 500, 1000, and 1500 mg were as follows: C_max were (742±253), (1355±502), and (2329±890) ng/mL, respectively; AUC_0-48 were (9072±3400), (16574 ± 6806) , and (29324±10857) ng·mL^-1·h,AUC_0-∞ were (9827±3152),(16882±6791), and (29924±10706) ng·mL^-1·h; t_max were (5.3±1.4), (4.2±1.2), and (5.9±2.8) hours; t_1/2 were (6.4±3.3), (6.4±3.5), and (6.7±4.3) hours.CONCLUSION: In this group of healthy Chinese subjects, AUC and C_max increased proportionally with the dose, the PK properties of ranolazine were linear after administration of single oral doses of 500 to 1500 mg.These dosages were generally well tolerated by all the subjects.

Key words: Ranolazine, Pharmacokinetics , LC-MS/MS