Study on pharmacokinetics of NiKeAn in rat

Abstract

Objective To develop a sensitive and specific high performance liquid chro matography (HPLC) method for determination of NiKeAn in rat plasma,and study the Pharmacokinetics in rat.Methods Sino chrom BDS column (250 mm×416 mm,5 μm)was used.The mobile phase was CH3OH-0.02％-phosphoric acid(10∶90)with a flow rate of 1.0 ml/min,and the detection wave length was at 260 nm and 30 ℃ column temperature.The plasma was analyzed after a simple protein precipitation procedure with acetonitrile.The blood sample was collected from retinal vein and involved protein precipitation with acetonitrile.Concentration of NiKeAn in rat blood was analyzed by the established method,and the pharmacokinetics parameters were calculated by the DAS2.0 software.Results The linear range of NiKeAn in rat plasma was 20-1000 μg/ml (r=0.9998).As concentration of NiKeAn in rat plasma were 50,150 and 500 μg/ml,the relative standard deviation of intra-batch and inter-batch were both less than 5.0％.The recovery rates of NiKeAn were 84.9％,81.9％ and 79.1％,respectively.After single dose of 125 mg/kg in rat,the main pharmacokinetic parameters were estimated to be as follows:elimination half-life time (t1/2β)was (32.99±23.14)min,the area under the curve (AUC) (0-t)was (14390.23±2584.02)mg· L-1· min,AUC (0-∞)was (16569.89±3450.31)mg· L-1 · min,the time of peak (Tmax)was (27.0±6.7)min,the peak concentration of drug (Cmax) was (242.13±33.89)mg/L.After single dose of 250 mg/kg in rat,the main pharmacokinetic parameters were estimated to be as follows:t1/2β was (59.05± 16.34)min,AUC (0-t) was (26752.23 ±7967.03) mg· L-1 · min,AUC (0-∞) was (35812.87 ±9476.48) mg· L-1 ·min,Tmax was (27.5±11.3) min,Cmax was (316.32±63.68) mg/L.After single dose of 500 mg/kg in rat,the main pharmacokinetic parameters were estimated to be as follows:t1/2β was (69.06±0.62)min,AUC (0-t)was (77306.48±27878.03) mg· L-1· min,AUC (0-∞)was (88014.22±26960.89)mg· L 1· min,Tmax was(40.0±7.7)min,Cmax was(601.42±147.15)mg/L.Conclusions The operation of established HPLC approach was simple,accurate,high-sensitive and better reproducible.This study provides a better reference for pharmacokinetics of NiKeAn in human bodies. Key words: Radiation-sensitizing agents; Niacinamide; Chromatography, high pressure liquid; Pharmacokinetics; Rats