ABSTRACT
Objective To establish a quick method to analyze vinorelbine ( NVB) in plasma of beagle dogs and study its pharmacokinetics of long-circulation and thermosensitive liposome loaded vinorelbine bitartrate.Methods The plasma was treated with liquid-liquid extraction after precipitation in methanol.The analysis was perfomed on a Venusil XBP C18 column(2.1 mm ×50 mm, 3 μm) at 35℃,the mobile phase consisted of methanol and water( containing 10 mmol/L ammonium acetate, 1%acetonitrile) 80∶20 and injection volume was 10μl.The type of mass spectrum was multireactive monitoring(MRM) in a positive mode.The monitor transitions were m/z 779.4-765.4 for vinorelbine and m/z 825.4-122 for vincristine.Results The concentration range from 10 to 2500 ng/ml had a good linearity ( r=0.0994).The precision, accuracy and extraction efficiency were acceptable.The plasma samples were stable for 10 days at -20℃ and 24 h at room temperature.Pharmacokinetic study in beagle dogs showed that the main parameters for injection and liposome were Cmax(833.51 ±150.42) and (1397.95 ±443.05)ng/ml, AUC(0-t) (577.16 ±223.57) and (1059.82 ±408.27) ng/ml· h, Cl(3014.64 ±1049.17)and 1633.10 ±551.77 ml/(h· kg), respectively.Conclusion A reliable HPLC-MS/MS method for vinorelbine analysis is established and can be applied to the pharmacokinetics study of liposome.The results show that liposome has a higher AUC, Cmax and longer Cl than injection.Meanwhile, liposome has a lower irritability.