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To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of crizotinib in human plasma and apply this method to determine its concentration in patients with non-small cell lung cancer after administrating.
Osimertinib was employed as the internal standard. The plasma samples were performed through protein precipitation with acetonitrile and chromatographed on Agilent Eclipse XDB C18 (2.1 mm×100.0 mm, 3.5 μm), mobile phase was consisted of acetonitrile containing 0.1% formic acid - 10 mmol·L-1 ammonium acetate containing 0.1% formic acid, flow rate was 0.25 mL·min-1, the column temperature was 30 ℃. The whole analytical time was 3 min. The detection was performed by positive ion electrospray ionization in multiple reaction monitoring mode, the quantitative analysis ion pairs were m/z 450.1→259.2 and m/z 500.2→72.1. The specificity, standard curve and lower limit of quantitation, precision and recovery, stability, matrix effect and residual effect of the method were investigated. After full validation, the method was applied to the determination of crizotinib in human plasma.
Good linearity was observed over the concentration range of 10.0-2 500.0 μg·L-1, the calibration curve was y=4.54×10-3x+3.22×10-2 (r=0.992 7). The accuracies were between 97.66%-105.55%. The relative standard deviation of inter-day and intra-day precision were less than 8.49%. The average recoveries and matrix effects were between 80.10%- 86.05% and 95.22%-110.66%.
The LC-MS/MS method is developed which meets the requirements of biological sample analysis and it can quickly, accurately monitor the concentration of crizotinib.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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