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目的应用液相色谱质谱联用(HPLC-MS/MS)建立长春瑞滨(NVB)比格犬血浆检测方法并用于药代动力学研究。方法血浆样品采用蛋白沉淀和液-液萃取方法。色谱柱Venusil XBP C18(2.1 mm×50 mm,3μm),柱温30℃,流动相∶水(10 mmol/L乙酸铵,1%乙腈)∶甲醇=20∶80,流速0.3 ml/min,进样量5μl;采用正离子模式、电喷雾离子源(ESI)及多反应监测(MRM),NVB m/z 779.4~765.4,内标长春新碱m/z 825.4~122。结果 NVB在5~2500 ng/ml浓度范围线性良好(r=0.9994),准确度、精密度和提取回收率符合方法学验证要求,样品在-20℃和室温放置稳定性良好。比格犬给药后,Cmax分别为(833.51±150.42)和(1397.95±443.05)ng/ml、AUC(0-t)分别为(577.16±223.5)和(1059.82±408.27)ng/ml·h,Cl分别为(3014.64±1049.17)和(1633.10±551.77)ml/(h·kg)。显著性检验表明,两种制剂的Cmax、AUC(0-t)、AUC(0-∞)和Cl均有显著性差异(P≤0.05)。结论建立了准确、灵敏、可靠的定量检测比格犬血浆中NVB分析方法,可满足药代动力学研究。脂质体能提高药物达峰浓度,延长药物半衰期,增加药物暴露强度并降低毒性反应。
Objective To establish a plasma assay for vinorelbine (NVB) beagle dogs using liquid chromatography-mass spectrometry (HPLC-MS / MS) and to study its pharmacokinetics. Methods Plasma samples were prepared by protein precipitation and liquid-liquid extraction. The column was Venusil XBP C18 (2.1 mm × 50 mm, 3 μm). The column temperature was 30 ℃. The mobile phase was water (10 mmol / L ammonium acetate, 1% acetonitrile) The volume of sample was 5μl. Positive ion mode, electrospray ionization (ESI) and multi-reaction monitoring (MRM) were used. NVB m / z 779.4-765.4 and internal standard vincristine m / z 825.4-122. Results NVB had a good linearity (r = 0.9994) at a concentration range of 5-2500 ng / ml. The accuracy, precision and extraction recovery met the validation requirements of methodology. The stability of NVB at -20 ℃ and room temperature was good. The Cmax were (833.51 ± 150.42) and (1397.95 ± 443.05) ng / ml, and the AUC (0-t) were (577.16 ± 223.5) and (1059.82 ± 408.27) ng / Cl were (3014.64 ± 1049.17) and (1633.10 ± 551.77) ml / (h · kg), respectively. Significant test showed that the two formulations of Cmax, AUC (0-t), AUC (0-∞) and Cl were significantly different (P ≤ 0.05). Conclusion The accurate, sensitive and reliable quantitative detection of Beagle dog plasma NVB analysis method can be established to meet the pharmacokinetic study. Liposomes can increase peak drug concentration, prolong drug half-life, increase drug exposure and reduce toxicity.