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A Validated 2D-LC-UV Method for Simultaneous Determination of Imatinib and N-desmethylimatinib in Plasma and Its Clinical Application for Therapeutic Drug Monitoring with GIST Patients

Author(s):

Houli Li, Di Zhang, Xiaoliang Cheng, Qiaowei Zheng, Kai Cheng, Lilong Xiong, Maoyi Wang, Weihua Dong and Weiyi Feng*   Pages 1 - 10 ( 10 )

Abstract:


Background: The trough concentration (Cmin) of Imatinib (IM) is closely related to the treatment outcomes and adverse reactions of patients with gastrointestinal stromal tumors (GIST). However, the drug plasma level has great interand intra-individual variability, and therapeutic drug monitoring (TDM) is highly recommended.

Objective: To develop a novel, simple, and economical two-dimensional liquid chromatography method with ultraviolet detector (2D-LC-UV) for simultaneous determination of IM and its major active metabolite, N-demethyl imatinib (NDIM) in human plasma, and then apply the method for TDM of the drug.

Method: Sample was processed by simple protein precipitation. Two target analytes were separated on the one-dimension column, captured on the middle column, and then transferred to the two-dimension column for further analysis. The detection was performed at 264 nm. The column temperature was maintained at 40˚C and the injection volume was 500 μL. Totally 32 plasma samples were obtained from patients with GIST who were receiving IM.

Method: Sample was processed by simple protein precipitation. Two target analytes were separated on the one-dimension column, captured on the middle column, and then transferred to the two-dimension column for further analysis. The detection was performed at 264 nm. The column temperature was maintained at 40˚C and the injection volume was 500 μL. Totally 32 plasma samples were obtained from patients with GIST who were receiving IM.

Conclusion: The novel 2D-LC-UV method is simple, stable, highly automated and independent of specialized technicians, which greatly increases the real-time capability of routine TDM for IM in hospital.

Keywords:

Imatinib, N-demethylimatinib, 2D-LC-UV, therapeutic drug monitoring, plasma, gastrointestinal stromal tumors.

Affiliation:

Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, School of Chemistry, Xi’an Jiaotong University, Xi’an, Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an



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