Imatinib is the first-line medication for the treatment of advanced gastrointestinal stromal tumor(GIST). Due to the large inter-individual variability, it is recommended to monitor the trough plasma concentration of ...Imatinib is the first-line medication for the treatment of advanced gastrointestinal stromal tumor(GIST). Due to the large inter-individual variability, it is recommended to monitor the trough plasma concentration of imatinib to ensure the efficacy and safety of imatinib therapy. In the present study, an HPLC-UV method was developed and validated for quantitating imatinib in the plasma of Chinese GIST patients. The samples were processed by protein precipitation and then mixed with a neutralizing agent(1.4 gK2CO3 and 0.65g KCl dissolved in 5mL ultrapure water). The chromatographic separation was performed on an Inert Sustain C18 column(250 mm×4.6 mm, 5 μM) maintained at 40 ℃ utilizing the mobile phase consisted of 25 m MNH4H2PO4(pH 8.0)–acetonitrile(61:39, v/v) at a flow rate of 1 m L/min, with an ultraviolet detector set at 265 nm. The method was fully validated according to the published guidelines. The plotted calibration curves were all linear within the range of 50 to 10 000 ng/m L. The validation results of the intra-day and inter-day accuracies and precisions ranged from –5.81% to 6.33%. The extraction recoveries were within the range of 92.38% to 97.86%. All the results of stability studies were all consistent with the acceptance criteria of within ±15%. Finally, the method was successfully applied to trough plasma concentration monitoring of imatinib in 150 Chinese GIST patients orally administrated with imatinib. Incurred sample reanalysis was conducted, results of which were also in accordance with the acceptance criteria of within ±20%.展开更多
文摘Imatinib is the first-line medication for the treatment of advanced gastrointestinal stromal tumor(GIST). Due to the large inter-individual variability, it is recommended to monitor the trough plasma concentration of imatinib to ensure the efficacy and safety of imatinib therapy. In the present study, an HPLC-UV method was developed and validated for quantitating imatinib in the plasma of Chinese GIST patients. The samples were processed by protein precipitation and then mixed with a neutralizing agent(1.4 gK2CO3 and 0.65g KCl dissolved in 5mL ultrapure water). The chromatographic separation was performed on an Inert Sustain C18 column(250 mm×4.6 mm, 5 μM) maintained at 40 ℃ utilizing the mobile phase consisted of 25 m MNH4H2PO4(pH 8.0)–acetonitrile(61:39, v/v) at a flow rate of 1 m L/min, with an ultraviolet detector set at 265 nm. The method was fully validated according to the published guidelines. The plotted calibration curves were all linear within the range of 50 to 10 000 ng/m L. The validation results of the intra-day and inter-day accuracies and precisions ranged from –5.81% to 6.33%. The extraction recoveries were within the range of 92.38% to 97.86%. All the results of stability studies were all consistent with the acceptance criteria of within ±15%. Finally, the method was successfully applied to trough plasma concentration monitoring of imatinib in 150 Chinese GIST patients orally administrated with imatinib. Incurred sample reanalysis was conducted, results of which were also in accordance with the acceptance criteria of within ±20%.
