Quantitative determination of ganoderic acid T in rat plasma by a sensitive RP-HPLC method and its application in pharmacokinetic studies

高效液相色谱法测定大鼠血浆中灵芝酸单体T及其药动学考察(英文)

A selective and sensitive HPLC method has been developed and validated for the quantification of ganoderic acid T in rat plasma. A reverse-phase column was used with UV detection at 245 nm. The mobile phase consisted of methanol-water-acetic acid （95.5：4.5：0.5, v/v/v） run at a flow rate of 1 mL/min. Testosterone propionate was used as the internal standard. The standard curve was linear over the range of 0.05-50 ~tg/mL in rat plasma with a linear correlation coefficient greater than 0.999. The lower limit of quantification of this assay was 20 ng/mL. The recoveries of samples at 0.05, 2 and 40 μg/mL were 97.6%, 98.4% and 103.2%, respectively. The relative standard deviations of intra- and inter-day assay variations were less than 8.2%. The usefulness of the assay was confirmed by the successful analysis of plasma samples from a pharmacokinetics study in rats. Following a single dose of ganoderic acid T （5 mg/kg for i.v. or 14 mg/kg for p.o.）, the main pharmacokinetic parameters by intravenous injection were： t1/2α （5.46±1.25） min; t1/2β：（227.18±11.40） min; CL： （1.09±0.16） mL/（kg·min）; A UC0-12 h： （3939.13±311.14） μg.min/mL; AUC0-12h （4681.96±710.70）μg.min/mL and the absolute bioavailability was 41.98%±2.40%. This method is simple, sensitive, and accurate. It is suitable for pharmacokinetic studies of ganoderic acid in rats.

建立大鼠血浆中灵芝酸单体T的高效液相色谱测定方法,并应用于其药动学研究。采用反相色谱柱,检测波长为245 nm,流动相为甲醇-水-乙酸(95.5:4.5:0.5,v/v/v);流速为1 mL/min;内标为丙酸睾酮。灵芝酸单体T血浆浓度在0.05～50μg/mL范围内线性良好(r>0.999),定量限为20ng/mL,低、中、高浓度质控样品回收率分别为97.6%,98.4%和103.2%,日内、日间精密度(以相对标准偏差表示)不超过8.2%。大鼠静脉给药主要药动学参数为:t_(1/2α):(5.46±1.25)min;t_(1/2β):(227.18±11.40)min;CL:(1.09±0.16)mL/(kg·min);AUC_(0-12h):(3939.13±311.14)μg·min/mL;AUC_(0-∞):(4681.96±710.70)μg·min/mL,绝对生物利用度为41.98%±2.40%。该方法快速简便、灵敏度高、定量准确,适用于大鼠体内灵芝酸的药物动力学研究。