上海医药
上海醫藥
상해의약
SHANGHAI MEDICAL & PHARMACEUTICAL JOURNAL
2015年
11期
70-74
,共5页
马晨%向志雄%万惠新%刘基晔%夏广新
馬晨%嚮誌雄%萬惠新%劉基曄%夏廣新
마신%향지웅%만혜신%류기엽%하엄신
酪氨酸激酶抑制剂%药代动力学%LC-MS/MS
酪氨痠激酶抑製劑%藥代動力學%LC-MS/MS
락안산격매억제제%약대동역학%LC-MS/MS
tyrosine kinase inhibitors%pharmacokinetics%LC-MS/MS
目的：建立定量测定大鼠血浆中抗肿瘤药aSPH0396的LC-MS/MS方法，并将其应用于大鼠体内药代动力学研究。方法：血浆样品在Waters BEH C18柱上以0.1%甲酸水溶液-0.1%甲酸乙腈溶液进行梯度洗脱；采用MRM方式进行定量测定，监测离子对为m/z553.4→453.4（SPH0396）和m/z 533.3→259.9（内标ponatinib）。结果：SPH0396在1.11～2488.50 ng/ml的浓度范围内呈良好的线性关系（R2=0.999），定量下限为1.11 ng/ml，回收率和精密度均符合生物样品检测要求。大鼠静注3 mg/kg SPH0396后，t1/2为3.43±0.37 h，CL为2.13±0.21L/h·kg，Vdss为6.76±0.26 L/kg。大鼠口服5、15和50 mg/kg的SPH0396后吸收较慢，Tmax为4～6 h。大鼠口服不同剂量的SPH0396，Cmax和AUC(0-t)的增加比例均高于剂量增加比例，生物利用度分别为17.15%、25.58%和36.19%。结论：本研究首次建立了特异、灵敏、便捷的定量检测大鼠血浆中SPH0396的LC-MS/MS方法，并成功应用于SPH0396的大鼠药代动力学研究。
目的：建立定量測定大鼠血漿中抗腫瘤藥aSPH0396的LC-MS/MS方法，併將其應用于大鼠體內藥代動力學研究。方法：血漿樣品在Waters BEH C18柱上以0.1%甲痠水溶液-0.1%甲痠乙腈溶液進行梯度洗脫；採用MRM方式進行定量測定，鑑測離子對為m/z553.4→453.4（SPH0396）和m/z 533.3→259.9（內標ponatinib）。結果：SPH0396在1.11～2488.50 ng/ml的濃度範圍內呈良好的線性關繫（R2=0.999），定量下限為1.11 ng/ml，迴收率和精密度均符閤生物樣品檢測要求。大鼠靜註3 mg/kg SPH0396後，t1/2為3.43±0.37 h，CL為2.13±0.21L/h·kg，Vdss為6.76±0.26 L/kg。大鼠口服5、15和50 mg/kg的SPH0396後吸收較慢，Tmax為4～6 h。大鼠口服不同劑量的SPH0396，Cmax和AUC(0-t)的增加比例均高于劑量增加比例，生物利用度分彆為17.15%、25.58%和36.19%。結論：本研究首次建立瞭特異、靈敏、便捷的定量檢測大鼠血漿中SPH0396的LC-MS/MS方法，併成功應用于SPH0396的大鼠藥代動力學研究。
목적：건립정량측정대서혈장중항종류약aSPH0396적LC-MS/MS방법，병장기응용우대서체내약대동역학연구。방법：혈장양품재Waters BEH C18주상이0.1%갑산수용액-0.1%갑산을정용액진행제도세탈；채용MRM방식진행정량측정，감측리자대위m/z553.4→453.4（SPH0396）화m/z 533.3→259.9（내표ponatinib）。결과：SPH0396재1.11～2488.50 ng/ml적농도범위내정량호적선성관계（R2=0.999），정량하한위1.11 ng/ml，회수솔화정밀도균부합생물양품검측요구。대서정주3 mg/kg SPH0396후，t1/2위3.43±0.37 h，CL위2.13±0.21L/h·kg，Vdss위6.76±0.26 L/kg。대서구복5、15화50 mg/kg적SPH0396후흡수교만，Tmax위4～6 h。대서구복불동제량적SPH0396，Cmax화AUC(0-t)적증가비례균고우제량증가비례，생물이용도분별위17.15%、25.58%화36.19%。결론：본연구수차건립료특이、령민、편첩적정량검측대서혈장중SPH0396적LC-MS/MS방법，병성공응용우SPH0396적대서약대동역학연구。
Objective:To develop and validate an LC-MS/MS method for the quantitative analysis of a new anti-tumor candidate SPH0396 in rat plasma so as to be applied to the pharmacokinetic study in rats.Methods:The chromatographic separation of SPH0396 was performed on BEH C18column by a gradient elution with water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid. The MS detection was conducted on MRM mode and the ion-pairs monitored were m/z553.4→453.4 (SPH0396) andm/z 533.3→259.9 with ponatinib as an internal standard.Results: A standard curve for the determination of SPH0396 showed a good linearity over the range of 1.11~2 488.50 ng/ml (R2=0.999) with the lower limit of quantiifcation at 1.11 ng/ml. The recovery and precision could meet the requirement of bioanalysis. After intravenous administration of SPH0396, the t1/2,CL and Vdss in rats were 3.43±0.37 h, 2.13±0.21 L/h·kg and 6.76±0.26 L/kg, respectively. The absorption of SPH0396 in rats was slow after oral administration. The peak level was reached at 4~6 h. The oral bioavailability was 17.15%, 25.58% and 36.19% at different doses, respectively.Conclusion:The LC-MS/MS method is speciifc, sensitive, rapid and simple and is suitable for pharmacokinetic study of SPH0396 in rats.
