Objective: To establish an HPLC-MS method for determination of three diastereoisomers in nirmatrelvir API. Methods: The analytical column was an InfinityLab Poroshell SB-C18 (150 mm×3.0 mm,2.7 μm), the two columns connected in series in series. The mobile phase was buffer (0.1% formic acid) (A) -acetonitrile (B), the diluent was water-acetonitrile-methanol (61 ∶ 19.5 ∶ 19.5). The whole run carried out by gradient elution. The column temperature was 80 ℃,the injection volume was 2 μL, and the sample temperature was 5 ℃. Results: Nirmatrelvir was separated completely from three diastereoisomers (the resolution>1.5). The test solution was stable for at least 3 d. The LOQ of diastereoisomer 1 was 0.04%, the LOQ of diastereoisomer 2 was 0.04%, the LOQ of diastereoisomer 3 was 0.05%. The linear correlation coefficient of diastereoisomer 3 was >0.99. The linear range was LOQ-150% of specification. The average recovery (n=9) of diastereoisomer 3 was 97.2%, RSD = 3.1%. The repeatability and intermediate precision completely met the requirements. The three diastereoisomers contents in three batches of nirmatrelvir API 24 months long-term stability test were all completely met the requirements, respectively. Conclusion: This method is simple, rapid, sensitive and specific to be used for the determination of three diastereoisomers in nirmatrelvir API.
JIN Yun
,
ZHANG Xian-hua
,
WANG Jun
,
LI Jin-xia
,
WU Yao-li
,
SHEN Meng-jie
,
ZHAO Long-shan
. Determination of three diastereoisomers in nirmatrelvir API by HPLC-MS[J]. Chinese Journal of Pharmaceutical Analysis, 2025
, 45(1)
: 175
-180
.
DOI: 10.16155/j.0254-1793.2024-0155
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