Quantitative LC-MS/MS method for nivolumab in human serum using IgG purification and immobilized tryptic digestion

被引:11
作者
Abe, Kazuki [1 ]
Shibata, Kaito [1 ]
Naito, Takafumi [1 ]
Karayama, Masato [2 ]
Hamada, Etsuko [3 ]
Maekawa, Masato [3 ]
Yamada, Yasuhide [2 ]
Suda, Takafumi [4 ]
Kawakami, Junichi [1 ]
机构
[1] Hamamatsu Univ Sch Med, Dept Hosp Pharm, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan
[2] Hamamatsu Univ Sch Med, Dept Clin Oncol, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan
[3] Hamamatsu Univ Sch Med, Dept Lab Med, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan
[4] Hamamatsu Univ Sch Med, Dept Internal Med, Div 2, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan
基金
日本学术振兴会;
关键词
CELL LUNG-CANCER; ABSOLUTE QUANTIFICATION; MONOCLONAL-ANTIBODY; PROTEIN; TRYPSIN; ENZYME; IMMUNOASSAYS; DENOSUMAB; STRATEGY; PLASMA;
D O I
10.1039/c9ay02087j
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
A liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method is a novel approach for the quantification of therapeutic monoclonal antibody. However, this method has severe ionization suppression and time-consuming sample preparation. In the present study, we developed a simple and rapid LC-MS/MS method for quantifying serum nivolumab with good analytical performance using immunoglobulin G (IgG) purification and immobilized tryptic digestion. Surrogate peptide derived from nivolumab was identified by a hybrid quadrupole-Orbitrap mass spectrometer. IgG purification and immobilized tryptic digestion were completed within 25 minutes. The chromatographic separation was completed in 10 minutes with stepwise-gradient elution. Chromatographic peaks interfering with the surrogate peptide and its stable isotope-labeled peptide as an internal standard were not observed from serum digests. The dynamic range of the calibration curve was 2-200 mu g mL(-1). The intra- and inter-assay accuracies and imprecisions were 92.2-104.5% and less than 10.0%, respectively. Serum nivolumab concentrations ranged from 12-112 mu g mL(-1) in 14 cancer patients. The measured concentrations in the LC-MS/MS method were strongly correlated with those in the ELISA method (r = 0.92, P < 0.01). In conclusion, a simple and rapid LC-MS/MS method for quantifying serum nivolumab using immobilized tryptic digestion coupled to IgG purification was found to be acceptable for clinical settings.
引用
收藏
页码:54 / 62
页数:9
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