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目的:建立一种稳定、灵敏的阿霉素靶向抗肿瘤前体化合物Z-GP-Dox的血药浓度检测方法,为进一步系统开展该候选化合物的体内药代动力学研究奠定方法学基础。方法:Z-GP-Dox血浆样品经过萃取剂乙腈-二氯甲烷(1∶4)液-液萃取后,采用HPLC-FD法检测。色谱柱为Zorbax SB-C18柱(150 mm×4.6 mm,5μm),柱温为25℃;流动相为乙腈-0.1%三氟乙酸(2∶3)等度洗脱,流速为1 mL.min-1。检测器为荧光检测器,激发波长为238 nm,发射波长为554 nm;内标为柔红霉素(DNR)。结果:利用所建立的HPLC-FD法测定大鼠血浆中Z-GP-Dox含量的线性范围为0.01～50μg.mL-1,r=0.999 5,相关回归方程:y=0.140 6x-0.048 3。该检测方法的日内精密度≤5%,日间精密度≤15%,萃取回收率≥83%。结论:本研究建立的Z-GP-Dox血药浓度测定方法有较高的准确度和灵敏度,适用于该候选化合物的体内药代动力学研究。
OBJECTIVE: To establish a stable and sensitive method for the determination of plasma concentration of doxorubicin-targeting antitumor precursor compound Z-GP-Dox in order to lay a foundation for further systematic study on the pharmacokinetics of this candidate compound. Methods: The plasma samples of Z-GP-Dox were extracted by liquid-liquid extraction with acetonitrile-methylene chloride (1: 4) and detected by HPLC-FD method. The column was a Zorbax SB-C18 column (150 mm × 4.6 mm, 5 μm) with a column temperature of 25 ° C. The mobile phase consisted of isocratic elution of acetonitrile-0.1% trifluoroacetic acid (2: 3) at a flow rate of 1 mL · min -1. The detector was a fluorescence detector with an excitation wavelength of 238 nm and an emission wavelength of 554 nm. The internal standard was daunorubicin (DNR). Results: The linear range of Z-GP-Dox in rat plasma was 0.01-50 μg.mL-1, r = 0.999 5 by HPLC-FD. The regression equation was y = 0.140 6x-0.048 3. The detection method of the day precision ≤ 5%, day precision ≤ 15%, extraction recovery ≥ 83%. Conclusion: The Z-GP-Dox assay established in this study has high accuracy and sensitivity and is suitable for in vivo pharmacokinetic studies of this candidate compound.