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HPLC Determination of Enantiomeric Purity of PF-04136309 Based on a Chiral Stationary Phase

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Abstract

A precise and sensitive LC method was developed and further validated for the determination of enantiomeric purity of (S)-N-[2-(3-{trans-4-hydroxy-4-[5-(pyrimidin-2-yl)pyridin-2-yl] cyclohexylamino} pyrrolidin-1-yl)-2-oxoethyl]-3-(trifluoromethyl) benzamide (PF-04136309). Baseline separation with a resolution higher than 1.8 was accomplished within 40 min using a CHIRALPAK AD (250 × 4.6 mm; particle size 5 μm) column, with n-hexane:2-propanol (70:30 v/v) as mobile phase at a flow rate of 1 mL min−1. The eluted analytes were subsequently detected with a UV detector at 260 nm. The effects of mobile phase components and temperature on enantiomeric selectivity as well as the resolution of enantiomers were thoroughly investigated. The calibration curves were plotted within a concentration range between 0.01 and 1 mg mL−1 (n = 9), and recoveries between 98.17 and 101.28 % were obtained, with relative standard deviation (RSD) lower than 1.44 %. The LOD and LOQ for PF-04136309 were 3.59 and 11.54 μg mL−1 and for its enantiomer were 3.39 and 11.28 μg mL−1, respectively. The developed method was demonstrated to be accurate, robust and sensitive for the determination of enantiomeric purity of PF-04136309, especially for the analysis of bulk samples.

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    Authors and Affiliations

    1. State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China

      Zeping Zuo, Mingxing Hu, Miaomiao Chen, Xiuli Chen, Fangfang Yang, Yinglan Zhao & Yiwen Zhang

    2. Sichuan Gooddoctor Panxi Pharmaceutical Co., Ltd., Chengdu, 610041, China

      Chenjuan Zeng

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    1. Zeping Zuo
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    2. Mingxing Hu
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    3. Miaomiao Chen
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    4. Xiuli Chen
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    5. Fangfang Yang
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    6. Chenjuan Zeng
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    7. Yinglan Zhao
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    Correspondence to Yinglan Zhao or Yiwen Zhang.

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    Z. Zuo and M. Hu contributed equally to this work.

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    Zuo, Z., Hu, M., Chen, M. et al. HPLC Determination of Enantiomeric Purity of PF-04136309 Based on a Chiral Stationary Phase. Chromatographia 78, 579–583 (2015). https://doi.org/10.1007/s10337-015-2860-8

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    • DOI: https://doi.org/10.1007/s10337-015-2860-8

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