Objective: To identify the structure and root cause of the unknown impurity in paroxetine hydrochloride tablet by LC-PDA-QTOF-MS. To prove the mechanism by forced degradation studies. To propose an effective control strategy to control the unknow impurity. Methods: The RRT 0.55 impurity that affected quality of the final product of paroxetine hydrochloride tablets were well separated from the main peak by optimizing the LC-MS chromatography conditions. The structure of RRT 0.55 impurity was confirmed by LC-MS/MS and UV absorption spectra by comparing the differences between those of paroxetine and RRT 0.55 impurity. The fragment peaks and generation pathway were analyzed. Structure of this impurity and the formation mechanism was verified with the structure-based forced studies. Results: The RRT 0.55 impurity was identified as a paroxetine-lactose adduct by LC-PDA-QTOF-MS/MS which was generated by the Maillard reaction between paroxetine with lactose. By optimizing the pH of the diluent in the sample preparation procedure of paroxetine hydrochloride tablets, this impurity was significantly decreased to lower than the reported limit in the final product (≤0.05%). Conclusion: The unknown RRT 0.55 impurity in paroxetine hydrochloride tablets is mainly resulted from the solution degradation in the process of sample preparation and it is not the true impurity in paroxetine hydrochloride tablets. By optimizing the pH of the diluent in the sample preparation procedure of paroxetine hydrochloride tablet, generation of this unknown peak can be controlled, and the true level of this unknown impurity can be determined in the modified method.
ZHOU Li-ping, LÜ Qian-qian, ZHENG Le-wei, ZHONG Xue-ni, WAN Heng, LI Min, LIN Jin-sheng
. Investigation of an unknown impurity in paroxetine hydrochloride tablets by LC-PDA-QTOF-MS in tandem with forced degradation studies*[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(9)
: 1608
-1617
.
DOI: 10.16155/j.0254-1793.2022.09.14
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