Affiliation:
1. Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
2. School of Chemistry, Xi’an Jiaotong University, Xi’an, China
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 inter- and 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 the ultraviolet detector (2D-LC-UV) for simultaneous determination of IM and its major
active metabolite, N-desmethyl imatinib (NDIM) in human plasma, and then apply the method
for TDM of the drug.
Methods:
The 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.
Results:
IM and NDIM were separated well from other impurities and the entire analytical time for
each run was 12.0 min. The calibration curves had good linearity in the range of 33.5-2678.4
ng/mL for IM, and 20.0-1600.0 ng/mL for NDIM, respectively. The extraction efficiency was more
than 95%. The acceptable accuracy, precision, recovery and stability were also obtained. The Cmin
of the drug in patients was measured with the validated method.
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.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmaceutical Science,Molecular Medicine,Biochemistry,Biophysics