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目的建立柱前衍生化HPLC/FLD法测定SD大鼠血浆中环维黄杨星D(CB)的含量,考察SD大鼠口服灌胃给予CB磷脂复合物(CBPC)药代动力学特征。方法以溶剂挥发法制备CBPC。采用星点设计优化制备工艺,以磷脂/CB、主药浓度作为考察指标,以复合率为评价指标。雄性SD大鼠12只,随机分为2组,口服灌胃给予CBPC和CB(60mg/kg,以CB计)后,分别在15min、30min、1、2、3、4、5、6、8、12、24h等时间点于大鼠眼底静脉丛取血,以HPLC/FLD法测定血浆中CB的浓度。采用C_(18)色谱柱(250mm×4.6mm,5μm),以甲醇-水(85∶15)为流动相,流速1.0mL·min~(-1),荧光检测激发波长231nm,发射波长385nm,柱温25℃。结果CBPC和CB的主要药动学参数如下:AUC_(0-t)为(1 703.81±549.38)μg·h·L~(-1)和(619.93±75.67)μg·h·L~(-1);T_(max)为(6.00±0)h和(4.33±0)h;C_(max)为(82.32±9.55)μg·L~(-1)和(69.27±8.66)μg·L~(-1)。CBPC的相对生物利用度为274.84%。结论磷脂复合物提高了CB的大鼠口服生物利用度。
OBJECTIVE To establish a pre-column derivatization HPLC / FLD method for the determination of cyclophosphamide D (CB) in plasma of SD rats and investigate the pharmacokinetics of CB phospholipid complex (CBPC) in SD rats. Methods CBPC was prepared by solvent evaporation method. Adopting the star design to optimize the preparation process, the phospholipid / CB, the concentration of the main drug as the inspection index, the composite rate as the evaluation index. Twelve male SD rats were randomly divided into two groups. After intragastric administration of CBPC and CB (60mg / kg, calculated as CB), rats were randomly divided into two groups: 15min, 30min, 1,2,3,4,5,6,8 , 12,24h and other time points in the rat venous plexus blood, HPLC / FLD method for the determination of plasma concentrations of CB. The mobile phase consisted of methanol and water (85:15) at a flow rate of 1.0 mL · min -1 on a C 18 column (250 mm × 4.6 mm, 5 μm). The excitation wavelength was 231 nm and the emission wavelength was 385 nm. Column temperature 25 ℃. Results The main pharmacokinetic parameters of CBPC and CB were as follows: AUC 0-t was (1 703.81 ± 549.38) μg · h · L -1 and 619.93 ± 75.67 μg · h · L -1 ); T max was (6.00 ± 0) h and (4.33 ± 0) h; C max was (82.32 ± 9.55) μg · L -1 and (69.27 ± 8.66) μg · L -1 -1). The relative bioavailability of CBPC was 274.84%. Conclusion Phospholipid complexes increase the oral bioavailability of CB in rats.