Objective: Chiral control plays an important role in development of stereoisomeric drugs. Due to the complexity and lack of predictability of chiral separation, column screening is still the gold standard to start the development of chiral methods for active pharmaceutical ingredients (APIs) and synthetic intermediates. Chiral reversed-phase liquid chromatography(RPLC) has been favored by other methods because of its universality in various matrices. Methods: The chiral drug database and the chiral screening database of APIs or intermediates were constructed and analyzed, with a total of 3 401 entries. A chiral RPLC screening strategy based on layer was established. Results: Seven-teen kinds of polysaccharide chiral stationary phases and 4 kinds of mobile phases were screened by gradient elution. Ten chiral solid phases(CSPs) containing two mobile phases(MPs) were selected and 82% of the screens were successfully separated. Two chiral RPLC screening layers (layer 1: AZ, OD, ID and IG) and (layer 2: AY, OJ, OZ, IA, IC and IH) and two MPs were proposed to make the hit rate of layer 1 reach 70% and the hit rate of combination set reach 80%. Conclusion: A relatively simple and efficient screening strategy of polysaccharide chiral reversed phase liquid chromatography is established, and the system can report automatically and has good applicability.
CHEN Yong-jun, DAI Li-na, BI Yi-cheng
. Evaluation of polysaccharide based chiral reversed phase liquid chromatography screening strategy in drug analysis*[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(12)
: 2038
-2043
.
DOI: 10.16155/j.0254-1793.2023.12.07
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