摘要
目的:建立正常人血浆中美索巴莫的 HPLC 测定法,并研究美索巴莫的分散片、干混悬剂与普通片在正常人体的相对生物利用度。方法:血浆样品用18%高氯酸沉淀后离心,上清液直接进样,以甲醇-25 mmol·L^(-1)磷酸二氢钠溶液(32:68,v/v)为流动相,在 Hypersil BDS_2柱(4.6 mm×200 mm,5 μm)上分离,流速为1.2 mL·min^(-1),检测波长为272 nm。18名健康志愿者以3周期随机交叉试验设计,分别单剂量口服美索巴莫分散片(T_1)、美索巴莫干混悬剂(T_2)或美索巴莫片(R)后不同时间点采血,测定血药浓度,计算药物动力学参数并进行生物等效性判定。结果:美索巴莫在0.081～20.8μg·mL^(-1)范围内浓度与峰面积的线性关系良好,同归方程为4=5.337×10~3C-191.9,r=0.9999。最小可定量浓度为0.081μg·mL^(-1),方法回收率为99.0%～106.2%(n=5),日内 RSD 为1.4%～6.8%(n=5);日间 RSD 为2.9%～6.8%(n=15)。单次服用 T_1、T_2或 R0.5 g 后,与 R 相比,T_1的相对生物利用度为(105.2±15.1)%;T_2的相对生物利用度为(105.6±14.3)%。药动学参数经多因数方差分析显示周期间与制剂间差异均无显著意义(P>0.05),双单侧 t 检验表明接受 T_1、T_2与 R 生物等效的假设,经计算90%置信区间均在规定值内。结论:该方法简单、快速,准确度、灵敏度高,重现性好,可用于美索巴莫在人体内过程研究;T_1、T_2与 R 为生物等效制剂。
Objective ：To establish an HPLC method for the determination of methocarbamol in human plasma and to study the bioequivalence of three methocarbamol formulations in healthy volunteers. Methods ： The samples were analyzed on a Hypersil BDS2 column（4.6 mm × 200 mm,5μm）followed with protein precipitated with 18% perchloric acid and detected at 272 nm. The mobile phase was methanol - sodium dihydrogen phosphate（25 mmol · L^-1） （32： 68,v/v）with a 1.2 mL · min^-1 flow rate. A single dose of 0. 5 g of methocarbamol dispersible tablets （T1 ） ,suspension（T2 ） or tablets （R） were given to 18 healthy volunteers in an open randomised crossover study, plasma samples were obtained at different times after administration, methocarbamol in plasma was determined by the newly - developed HPLC method, and then the pharmacokinetics and bioavailability were studied. Results： Methocarbamol was separated well from endogenous substance, and the regressive curve （A = 5. 337 × 10^3 C - 191.9,r =0. 9999）was linear within the range of 0. 081 μg · mL^-1 to 20.8 μg · mL^-1 ,the method recoveries from plasma were in the range of 99.0% - 106.2% （n = 5 ） , inter - day RSD and intra - day RSD respectively were in the range of 1.4% -6. 8% （n = 5 ）and 2.9% -6. 8% （n = 15 ）. When compared with R, the relative bioavailability of T1 and T2 were（ 105.2 ± 15.1 ）% and（ 105.6 ± 14. 3）% respectively. The result of analysis of variance and two one - side t - test statistical analysis showed that there were no significant differences among T1, T2 and R （ P 〉 0.05 ）. Conclusion： The established HPLC method is accuracy and sensible for plasma methocarbamol determination. T1 ,T2 and R are bioequivalent.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2008年第5期702-705,共4页
Chinese Journal of Pharmaceutical Analysis
