ABSTRACT
To investigate the pharmacokinetics of irinotecan hydrochloride (CPT-11) in rats and the tissue distribution of CPT-11 in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11 NPs) via tail veins, separately, a LC-MS/MS method was established to determine the concentration of CPT-11 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of CPT-11 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with CPT-11 solution, the elimination half-life of CPT-11 was prolonged from 2.28 h to 3.95 h after the intravenous injection of CPT-11 NPs, and its AUC was 1.47 times than that of CPT-11 solution. After the injection of CPT-11 NPs in mice, the concentrations of CPT-11 loaded in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, but lower in the spleen, liver, kidney and heart, but the least in brain. CPT-11 NPs could improve CPT-11 's AUC, and help CPT-11 to reach long circulation activity.
Subject(s)
Animals , Female , Male , Mice , Rats , Antineoplastic Agents, Phytogenic , Blood , Pharmacokinetics , Area Under Curve , Camptothecin , Blood , Pharmacokinetics , Chromatography, High Pressure Liquid , Injections, Intravenous , Nanoparticles , Random Allocation , Rats, Sprague-Dawley , Spectrometry, Mass, Electrospray Ionization , Tissue DistributionABSTRACT
<p><b>OBJECTIVE</b>The study aimed to develop the assay of chrysosplenetin (CHR), a metabolic inhibitor of artemisinin by UPLC-MS/MS in rat plasma and investigate the pharmacokinetics parameters of CHR.</p><p><b>METHOD</b>The plasma samples were precipitated by acetonitrile to remove the proteins. Separation was carried out on a Shim-pack XR-ODS C,18(2. 0 mm x 100 mm, 2. 2 micromp.m) column using a mobile phase containing methanol-0. 1% formic acid (87:13) using by diazepam as internal standard. Mass spectrometer with electrospray ionization (ESI) operated in the positive ion mode was used for analysis. Total analysis time was 2 min.</p><p><b>RESULT</b>The assay was linear in the range 5-5 000 microg L-1 (r =0. 999 3) with recoveries in the range from 69. 0% to 81.2% and satisfied inter-, intra- precision and accuracy. CHR after oral administration is not easy to absorb with double or multimodal peak phenomenon. The t1/2 of CHR after intravenous injection was very short and that of low, medium, and high dosage was (17. 01 +/- 8. 06) , (24. 62 +/- 4. 59), (28. 46+/- 4. 63) min, respectively.</p><p><b>CONCLUSION</b>The developed method was special, rapid, and sensitive for determination of CHR pharmacokinetics. [Key words] UPLC-MS/MS; chrysosplenetin; pharmacokinetics; plasma; rat</p>