| 引用本文: | 楼江,江洪,劳俊杰,陈玲,易成,邬欣梅,汪静,王刚.超高效液相色谱-串联质谱法测定人血浆中安罗替尼浓度的方法学研究及应用[J].中国现代应用药学,2024,41(11):37-46. |
| loujiang,Jiang Hong,Lao Jun-jie,Chen Ling,Yi cheng,Wu XIN-MEI,Wang Jing,Wang Gang.Quantitative analysis of anlotinib in human plasma by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry and assessment of clinical application[J].Chin J Mod Appl Pharm(中国现代应用药学),2024,41(11):37-46. |
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| 超高效液相色谱-串联质谱法测定人血浆中安罗替尼浓度的方法学研究及应用 |
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楼江,江洪,劳俊杰,陈玲,易成,邬欣梅,汪静,王刚
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杭州市第一人民医院
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| 摘要: |
| 目的：建立一种快速测定人血浆中安罗替尼浓度的超高效液相色谱-串联质谱法(UPLC-MS/MS)并评估临床应用。方法：以泽布替尼为内标物,血浆用乙腈蛋白沉淀,使用Ultimate XB-C18色谱柱 (100mm × 2.1mm, 3.0μm) 分离,流动相为10mM醋酸胺+0.1%甲酸和乙腈进行梯度洗脱,流速为0.6 mL/min,进样量为5μL。应用电喷雾离子化,正离子模式下用多反应模式监测安罗替尼(m/z 408.1→339.1)和内标物(m/z 472.2→290.1)的浓度,考察该方法学的专属性、定量下限与标准曲线、精密度与回收率、基质效应与稳定性及临床应用。结果：安罗替尼在1.0-100.0ng/ml线性关系良好,标准曲线为y=0.515148x+0.0144461(R2=0.9984),精密度RSD小于9%,回收率和基质效应分别是104.81-107.32% 和102.54%-104.26%,该方法稳定性良好、血浆基质对安罗替尼测定结果影响较小。本研究考察了52名服用安罗替尼单药治疗的非小细胞肺癌患者,采集服用安罗替尼治疗第43天的谷浓度血浆,并对其血药浓度进行测定,发现所有患者安罗替尼的血药浓度均高于1.0 ng/mL (最低定量下限),血药浓度均值±标准差是11.38± 4.29ng/mL,变异系数是37.66%,表现出较大的个体间差异。结论：本方法灵敏度高、专属性强、定量准确,适用于人血浆中安罗替尼的浓度监测。 |
| 关键词: 超高效液相色谱-串联质谱法 安罗替尼 血药浓度 |
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| 基金项目:浙江省自然科学(LGF21H31003); 浙江省医药卫生科技计划项目 (2021KY877); 浙江省药学会医院药学专项科研基金 (2022ZYY09)；医学科研发展临床与基础研究专项(B21077EN); |
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| Quantitative analysis of anlotinib in human plasma by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry and assessment of clinical application |
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loujiang1,2,3, Jiang Hong4,2,5, Lao Jun-jie4,2,5, Chen Ling4,2,5, Yi cheng4,2,5, Wu XIN-MEI4,2,5, Wang Jing4,2,5, Wang Gang4,2,5
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1.First people '2.'3.s Hospital of Hangzhou;4.Hangzhou First people'5.s hospital
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| Abstract: |
| Objective: To establish an ultra-high-performance liquid chromatography mass spectrum/mass spectrum (UPLC-MS/MS) method for the determination of anlotinib in human plasma and assessment of clinical application. Method: The internal standard using zanubrutinib and the extraction process was performed through protein precipitation method using acetonitrile, followed by separation on an Ultimate XB-C18 column (100mm × 2.1mm, 3.0μm) using acetonitrile and 10mM ammonium acetate-0.1% formic acid step-elution gradient. The flow rate was 0.6 mL/min and injection volume was 5μL. The mass analysis was performed by positive ion electrospray ionization in multiple-reaction monitoring mode, and the mass spectrometer was set at 408.1→339.1 for anlotinib and 472.2→290.1 for internal standard, respectively. The specificity, standard curve and lower limit of quantification, precision and recovery, matrix effect and stability of the method and clinical application were investigated. Results: The method was validated over the concentration range of 1.0-100.0 ng/ml, the calibration curve was y=0.515148x+0.0144461 (R2=0.9984). The precision was less than 9%, the recovery and matrix effect were 104.81-107.32% and 102.54%-104.26%, respectively, and this method has good stability and was not affected by matrix effect. The method has been used for determined 52 advanced non-small cell lung cancer (NSCLC) patients treated with anlotinib. The trough plasma concentration (Ctrough) was measured on day 43 after initiation of anlotinib treatment. Anlotinib Ctrough were higher than LLOQ (1.0 ng/ml) from 52 patients. The plasma concentration of anlotinib Ctroughwas 11.38 ± 4.29 ng/ml with 37.66% coefficients of variation, which were shown large inter-patient variability.Conclusion: This method was high sensitivity, specificity and accurate, and suitable for determination of anlotinib Ctroughin human plasma. |
| Key words: Ultra-high-performance liquid chromatography-mass spectrum/mass spectrum Anlotinib Human plasma |
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