| 274 | 1 | 81 |
| 下载次数 | 被引频次 | 阅读次数 |
目的建立一种快速、灵敏、准确的测定血浆中多柔比星浓度的固相萃取-超快速液相色谱-串联质谱联用(UFLC-MS/MS)方法。方法血浆样品经4%磷酸溶液提取后采用PRiME MCX萃取小柱净化,在Shim-pack XR-ODSⅡ柱(100 mm×2.0mm, 1.7μm)上,以含0.1%甲酸的水溶液(A相)和含0.1%甲酸的乙腈溶液(B相)为流动相进行梯度洗脱,以柔红霉素为内标,采用电喷雾离子源(ESI)在多反应监测(MRM)正离子模式下检测,多柔比星和内标的定量离子对分别为m/z544.3→397.0和m/z528.4→320.9,定性离子对分别为m/z 544.3→379.2和m/z 528.4→363.0。结果多柔比星在质量浓度0.2～200.0μg·L-1时具有良好的线性,定量检测下限(LLOQ)为0.2μg·L-1,其批内和批间RSD分别<10.7%和11.9%。相比Oasis HLB萃取小柱,PRiME MCX小柱的绝对基质效应平均值和提取平均回收率可分别提高14.3%和25.0%。结论采用PRiME MCX小柱,不仅可以降低基质效应提高回收率,而且可以缩短分析时间,简化操作程序。所建立的方法可用于患者血浆中痕量多柔比星的快速准确测定。
Abstract：AIM To establish a fast, sensitive and accurate method for the determination of doxorubicin in plasma sample by solid-phase extraction and ultrafast liquid chromatography tandem mass spectrometry(UFLC-MS/MS). METHODS The separation was carried out on a Shim-pack XR-ODS Ⅱ column(100 mm × 2.0 mm, 1.7 μm)using 0.1% formic acid-water solution and 0.1% formic acid-acetonitrile as mobile phase in gradient elution after plasma samples were extracted by 4% phosphoric acid solution and cleaned by PRiME MCX solid-phase extraction cartridge. Detection was performed by an electrospray ionization(ESI) in the positive multipile reaction monitoring(MRM) mode using daunorubicin as an internal standard(IS). The ion pairs m/z 544.3 → 397.0 and m/z 528.4 → 320.9 were selected for quantification for doxorubicin and IS, the ion pairs m/z 544.3 → 379.2 and m/z 528.4 → 363.0 were selected for qualitative analysis, respectively. RESULTS Within-batch and between-batch relative standard deviations were less than 10.7% and 11.9%, respectively. The linear range was 0.2-200.0 μg·L-1 for doxorubicin. The lower limit of quantification(LLOQ) in plasma sample was 0.2 μg·L-1. Compared to Oasis HLB extraction cartridge, the average values of absolute matrix effect and average extraction recovery of PRiME MCX cartridge increased by 14.3% and 25.0%, respectively. CONCLUSION The use of PRiME MCX cartridge can not only reduce absolute matrix effect and improve recovery, but also shorten the analysis time, simplify the operation process. The established method can be applied to rapid and accurate determination of trace doxorubicin in the patient's plasma sample.
[1]ZUPPINGER C,TIMOLATI F,SUTER T M.Pathophysiology and diagnosis of cancer drug induced cardiomyopathy[J].Cardiovasc Toxicol,2007,7(2):61.
[2]OCTAVIA Y,TOCCHETTI C G,GABRIELSON K L,et al.Doxorubicin-induced cardiomyopathy:from molecular mechanisms to therapeutic strategies[J].J Mol Cell Cardiol,2012,52(6):1213.
[3]STěRBA M,POPELOVáO,VáVROVáA,et al.Oxidative stress,redox signaling,and metal chelation in anthracycline cardiotoxicity and pharmacological cardioprotection[J].Antioxid Redox Signal,2013,18(8):899.
[4]马军,秦叔逵,沈志祥.蒽环类药物心脏毒性防治指南(2013年版)[J].临床肿瘤学杂志,2013,18(10):925.
[5]满爽,金艺,台晶杰,等.盐酸多柔比星脂质体注射液在Beagle犬体内的药动学及血红蛋白结合研究[J].沈阳药科大学学报,2018,35(4):295.
[6]权会丽,曹佳丽,程丽娟,等.HPLC法同时测定乳腺癌患者血浆中多柔比星、表柔比星及环磷酰胺的血药浓度[J].药物分析杂志,2020,40(7):1236.
[7]HAN J,ZHANG J,ZHAO H Y,et al.Simultaneous determination of doxorubicin and its dipeptide prodrug in mice plasma by HPLCwith fluorescence detection[J].J Pharm Anal,2016,6(3):199.
[8]DAEIHAMED M,HAERI A,DADASHZADEH S.A simple and sensitive HPLC method for fluorescence quantitation of doxorubicin in micro-volume plasma:applications to pharmacokinetic studies in rats[J].Iran J Pharm Res,2015,14(Suppl):33.
[9]杨俊凤,王旭光,李彬瑶,等.UPLC-MS/MS测定大鼠血浆多柔比星浓度方法的建立及毒代动力学应用[J].药物评价研究,2020,43(1):77.
[10]SEMREEN M H,ALNISS H Y,MOUSA M K,et al.Quantitative determination of doxorubicin in the exosomes of A549/MCF-7 cancer cells and human plasma using ultra performance liquid chromatography-tandem mass spectrometry[J].Saudi Pharm J,2018,26(7):1027.
[11]郑楠,王兴,王瑶琪,等.UPLC-MS/MS法分析新型多柔比星前药在肿瘤细胞中的浓度[J].药学学报,2018,53(2):278.
[12]李敬涛,王浩,孙严彤,等.HPLC-MS/MS法同时测定大鼠血浆中多柔比星及其代谢产物的浓度[J].中国临床药理学杂志,2020,36(2):193.
[13]SOTTANI C,LEONI E,PORRO B,et al.Validation of an LC-MS/MS method for the determination of epirubicin in human serum of patients undergoing drug eluting microsphere-transarterial chemoembolization (DEM-TACE)[J].J Chromatogr B Analyt Technol Biomed Life Sci,2009,877(29):3543.
[14]HE W X,MARTIN J H,SHAW P N,et al.A simple and sensitive LC-MS/MS method for the simultaneous determination of cyclophosphamide and doxorubicin concentrations in human plasma[J].Curr Pharm Anal,2017,14(1):53.
[15]XIE Y,SHAO N,JIN Y,et al.Determination of non-liposomal and liposomal doxorubicin in plasma by LC-MS/MS coupled with an effective solid phase extraction:In comparison with ultrafiltration technique and application to a pharmacokinetic study[J].JChromatogr B Analyt Technol Biomed Life Sci,2018,1072:149.
[16]SAKAI-KATO K,SAITO E,ISHIKURA K,et al.Analysis of intracellular doxorubicin and its metabolites by ultra-highperformance liquid chromatography[J].J Chromatogr B Analyt Technol Biomed Life Sci,2010,878(19):1466.
[17]MATUSZEWSKI B K,CONSTANZER M L,CHAVEZ-ENG CM.Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS[J].Anal Chem,2003,75(13):3019.
[18]国家药典委员会.中国药典：四部[S].北京：中国医药科技出版社，2020:466-471.
基本信息:
DOI：10.19577/j.1007-4406.2022.01.007
中图分类号:R969
引用信息:
[1]陈晓红,阮海东,陈天琪,等.固相萃取-UFLC-MS/MS法快速测定血浆中多柔比星浓度[J].中国临床药学杂志,2022,31(01):30-36.DOI:10.19577/j.1007-4406.2022.01.007.
基金信息:
宁波市医学重点学科建设计划（编号2022B18）; 宁波市自然科学基金（编号2019A610307）
2022-01-25
2022-01-25