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Journal of Chinese Pharmaceutical Sciences ›› 2020, Vol. 29 ›› Issue (9): 637-648.DOI: 10.5246/jcps.2020.09.059

• Original articles • Previous Articles     Next Articles

Development and validation of an HPLC-UV method for routine trough plasma concentration monitoring of imatinib in Chinese patients with gastrointestinal stromal tumor

Yi Zhou1, Junli Lai2, Feng Qiu1*, Jun Zhang2*   

  1. 1. Department of Pharmacy, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
    2. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
  • Received:2020-05-14 Revised:2020-07-06 Online:2020-09-30 Published:2020-08-16
  • Contact: Tel.: +86-23-89012410, E-mail: qiufeng.cn@gmail.com; zjun2323@sina.cn

Abstract:

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 g K2CO3 and 0.65 g KCl dissolved in 5 mL ultrapure water). The chromatographic separation was performed on an InertSustain C18 column (250 mm×4.6 mm, 5 µM) maintained at 40 ºC utilizing the mobile phase consisted of 25 mM NH4H2PO4 (pH 8.0)–acetonitrile (61:39, v/v) at a flow rate of 1 mL/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/mL. 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%.

Key words: Imatinib, HPLC, Gastrointestinal stromal tumor, Therapeutic drug monitoring, Incurred sample reanalysis

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