RP-HPLC法测定Beagle犬血浆中烟酸浓度及烟酸药代动力学研究

Determination of sustained-release niacin formulation by RP-HPLC in dog plasma and its pharmacokinetic study

目的:建立RP -HPLC法测定血浆中烟酸的药物浓度,并将建立的方法应用于Beagle犬测定烟酸缓释片的血药浓度,计算其药代动力学参数和相对生物利用度。方法:0 .1ml血浆样品经乙腈沉淀蛋白后直接进样;流动相为乙腈 水相(8 92 ) ,水相含10mmol·L-1磷酸二氢钾,用磷酸调pH值至4 .0 ,流速为1.0ml·min-1;色谱柱为汉邦科技LichrospherC18(5 μm,2 5 0mm×4 .6mmI .D .) ,检测波长为2 6 3nm。6只Beagle犬随机交叉口服5 0 0mg复方洛伐烟酸缓释片和5 0 0mg标准参比烟酸普通片后,用RP HPLC法测定血浆中烟酸的药物浓度。结果:分析方法符合生物样品分析要求。Beagle犬单剂量口服复方洛伐烟酸缓释片5 0 0mg后,估算的末端相t1 2 为1.3±1.2h ,Tmax为2 .3±0 .8h ,Cmax为35 .3±4 .9mg·L-1,MRT为3.5±0 .6h。复方洛伐烟酸缓释片的AUC、Cmax 明显低于烟酸普通片(P <0 .0 5 )。经配对t检验分析显示复方洛伐烟酸缓释片Tmax明显长于普通片(P <0 .0 5 )。结论:单剂量口服复方洛伐烟酸缓释片后,测得的Cmax和AUC与烟酸普通片均有显著性差异,受试缓释片的Tmax长于参比普通片,Cmax低于参比普通片,说明受试缓释片无突释现象,有一定的缓释效果。

AIM: To establish a simple RP-HPLC method for the determination of niacin in dog plasma and calculate the relative bioavailability and the pharmacokinetic parameters of sustained-release niacin formulation. METHODS: Niacin was extracted from dog plasma with perchloric acid. The RP-HPLC was performed on a Lichrospher C_ 18 column (5 μm, 250 mm× 4.6 mm I.D.) with mobile phase of acetonitrile -10 mmol·L -1 monopotassium phosphate (892, v/v), and the pH of the water phase was adjusted to 4.0 with phosphoric acid at flow rate of 1.0 ml·min -1. Niacin was detected by UV absorbance at 263 nm. Single dose of sustained-release niacin formulation (500 mg) and rapid-release niacin formulation (500 mg) were given to six Beagle dogs. RESULTS: The t_ 1/2, T_ max, C_ max and MRT of niacin in the sustained release formulation were 1.25± 1.15 h, 2.3± 0.8 h, 35.3± 4.87 mg·L -1 and 3.45± 0.55 h, respectively. The T_ max of sustained-release niacin formulation is significantly longer than that of the conventional niacin tablet (P< 0.05), the C_ max was significantly lower than that of the conventional niacin tablet (P< 0.05). CONCLUSION: This method is simple, accurate, sensitive and applicable for pharmacokinetic study of niacin. The relative bioavailability is ( 40.7± 8.6)% in the sustained-release formulation.