Objective:To establish an HPLC method for the analysis of related substances in (S)-2-(4-(4-(4-(6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl)piperidin-1-yl)phenyl)-1H-pyrazol-1-yl)ethan-1-ol (SHR9146), a novel high selective indoleanmine 2,3-dioxygenase(IDO1)/tryptophan 2,3-dioxygenaes(TDO) inhibitor used for tumor immunotherapy. Methods: The chromatographic separation was performed on a Kromasil C18 column (250 mm×4.6 mm, 5 μm) with gradient elution by 0.01 mol·L-1 monopotassium phosphate buffer (containing 0.1% triethylamine and adjusted pH to 3.0 with phosphate acid) and acetonitrile as mobile phase at a flow rate of 1.0 mL·min-1, and the UV detection wavelength was set at 270 nm. Results: The peaks of SHR9146 and related substances could be separated completely. UPLC-UV analysis could achieve a good linear regression in the concentration range of 0.01-5.0 μg·mL-1 (r>0.999). The detection limit and quantification limit of SHR9146 were 21.95 and 73.16 ng·mL-1 respectively. Using the HPLC method, the related substances of three batches were detected and calculated by using principal component self-control with correct factor, the total impurities were less than 1.0% with impurity SHR9146Z-399 in the range of 0.46%-0.60% and SHR9146Z-333 and other single impurity not more than 0.11% and 0.10% respectively. Conclusion: The established method has good specificity and high sensitivity, and can be used for the quality control of SHR9146.
XIAO Mei, LI Wei, ZHANG Ying-ying, YAO Fei, HANG Tai-jun
. Detection of related substances of SHR9146—a novel IDO1/TDO dual inhibitor[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(10)
: 1751
-1758
.
DOI: 10.16155/j.0254-1793.2023.10.13
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