中国医药导报
中國醫藥導報
중국의약도보
CHINA MEDICAL HERALD
2014年
35期
55-59
,共5页
张文萍%甘梦月%马妍妮%党宏万
張文萍%甘夢月%馬妍妮%黨宏萬
장문평%감몽월%마연니%당굉만
液相色谱-串联质谱%阿霉素%药动学研究%含量测定
液相色譜-串聯質譜%阿黴素%藥動學研究%含量測定
액상색보-천련질보%아매소%약동학연구%함량측정
LC-MS/MS%Doxorubicin%Pharmacokinetics%Determination
目的：建立液相色谱-串联质谱(LC-MS/MS)法测定大鼠血浆中阿霉素的血药浓度，并用于阿霉素载药纳米粒的体内药动学研究。方法色谱柱采用Shim-pack XR-ODS柱(2.0 mm×100 mm，2.2μm)，仪器采用API 4000三重四极杆串联质谱仪，采用多反应监测(multiple reaction monitoring，MRM)定量离子对为m/z544.2→m/z396.9(阿霉素)和m/z357.3→m/z133.8(吡格列酮，内标)；甲醇沉淀蛋白法处理样品。结果阿霉素在2.0~2000μg/L范围内线性关系良好，定量下限为2.0μg/L，血浆中的内源性物质不干扰阿霉素的测定；日内和日间精密度RSD均小于±15.0%；阿霉素低、中、高3个QC浓度的提取回收率分别为(92.1±5.9)%、(82.8±2.9)%和(80.1±9.7)%，基质效应分别为(91.1±2.4)%、(82.1±1.7)%和(81.2±2.5)%。结论该方法适用于阿霉素纳米粒在大鼠体内的药物动力学研究。
目的：建立液相色譜-串聯質譜(LC-MS/MS)法測定大鼠血漿中阿黴素的血藥濃度，併用于阿黴素載藥納米粒的體內藥動學研究。方法色譜柱採用Shim-pack XR-ODS柱(2.0 mm×100 mm，2.2μm)，儀器採用API 4000三重四極桿串聯質譜儀，採用多反應鑑測(multiple reaction monitoring，MRM)定量離子對為m/z544.2→m/z396.9(阿黴素)和m/z357.3→m/z133.8(吡格列酮，內標)；甲醇沉澱蛋白法處理樣品。結果阿黴素在2.0~2000μg/L範圍內線性關繫良好，定量下限為2.0μg/L，血漿中的內源性物質不榦擾阿黴素的測定；日內和日間精密度RSD均小于±15.0%；阿黴素低、中、高3箇QC濃度的提取迴收率分彆為(92.1±5.9)%、(82.8±2.9)%和(80.1±9.7)%，基質效應分彆為(91.1±2.4)%、(82.1±1.7)%和(81.2±2.5)%。結論該方法適用于阿黴素納米粒在大鼠體內的藥物動力學研究。
목적：건립액상색보-천련질보(LC-MS/MS)법측정대서혈장중아매소적혈약농도，병용우아매소재약납미립적체내약동학연구。방법색보주채용Shim-pack XR-ODS주(2.0 mm×100 mm，2.2μm)，의기채용API 4000삼중사겁간천련질보의，채용다반응감측(multiple reaction monitoring，MRM)정량리자대위m/z544.2→m/z396.9(아매소)화m/z357.3→m/z133.8(필격렬동，내표)；갑순침정단백법처리양품。결과아매소재2.0~2000μg/L범위내선성관계량호，정량하한위2.0μg/L，혈장중적내원성물질불간우아매소적측정；일내화일간정밀도RSD균소우±15.0%；아매소저、중、고3개QC농도적제취회수솔분별위(92.1±5.9)%、(82.8±2.9)%화(80.1±9.7)%，기질효응분별위(91.1±2.4)%、(82.1±1.7)%화(81.2±2.5)%。결론해방법괄용우아매소납미립재대서체내적약물동역학연구。
Objective To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the de-termination of Doxorubicin in rat plasma and application of pharmacokinetics study. Methods The chromatographic separation was carried out on an Shim-pack XR-ODS (2.0 mmí100 mm, 2.2μm) and detected by an API 4000 mass spectrometer. The compounds were quantified by multiple-reaction monitoring (MRM) mode using transition mass of m/z 544.2→m/z396.9 for doxorubicin and m/z 357.3→m/z 133.8 for pioglitazone (internal standard). Protein precipitation by methanol was used for the sample pretreatment. Results The calibration curves of Doxorubicin were linear over the range 2-2000μg/L with the lower limit of quantication of 2.0μg/L. Determination of Doxorubicin was not interfered by endogenous substance in plasma. The intra-day and inter-day precisions of QC samples were within±15.0% (RSD%). The extraction recoveries and matrix effects of QC samples were (92.1±5.9)%, (82.8±2.9)%, and (80.1±9.7)%; (91.1±2.4)%, (82.1±1.7)%, and (81.2±2.5)%, respectively. Conclusion This method can be applied to pharmacokinetic studies of Doxorubicin loaded nanoparticles in rats.
