Development of high-performance liquid chromatography assay for pharmacokinetic analysis of KCNQ/M-channel opener QO58-lysin in rat plasma

doi:10.5246/jcps.2014.03.019

Journal of Chinese Pharmaceutical Sciences

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Development of high-performance liquid chromatography assay for pharmacokinetic analysis of KCNQ/M-channel opener QO58-lysin in rat plasma

Tianyang Ma, Bochuan Teng, Jinlong Qi, Hailin Zhang, KeWei Wang^*

1. State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China
3. PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China

Received:2013-09-26 Revised:2013-10-31 Online:2014-03-13 Published:2013-11-06
Contact: *Corresponding author. Tel.: 86-10-82805605; E-mail: wangkw@bjmu.edu.cn
About author:*Corresponding author. Tel.: 86-10-82805605; E-mail: wangkw@bjmu.edu.cn
Supported by:
Ministry of Science and Technology of China (Grant No. 2013ZX09103001-015 and 2013CB531300), and the National Science Foundation of China (Grant No. 81221002).

Abstract

Abstract:

A simple, reliable and efficient assay for quantitative analysis of a novel Kv7/KCNQ/M-channel opener QO58-lysin in rat plasma was developed using high-performance liquid chromatography (HPLC) with UV detection. Separation of compound QO58-lysin from plasma was achieved using a reverse-phase C₁₈ column with a mobile phase of 0.2 M ammonium acetate in H₂O–acetonitrile (40:60, v/v) with nitrendipine used as an internal standard (IS). The retention times of QO58-lysin and the IS in rat plasma were 3.8 and 5.4 min, respectively. Calibration curve was linear ranging from 0.1 to 120 μg/mL with correlation coefficient (r²) of 0.9996. The lower limit of quantification was 0.1 μg/mL. Accuracy, precision, recovery as well as stability were all within acceptable criteria according to Food and Drug Administration (FDA) guidelines. This validated assay wassuccessfully applied to determine the pharmacokinetics of QO58-lysin administered intravenously (10 mg/kg) in SD rats. The distribution and elimination half-life of QO58-lysin in plasma was (0.25±0.16) h and (2.15±0.12) h, respectively.

Key words: KCNQ opener, QO58-lysin, HPLC, Pharmacokinetics

CLC Number:

R969.1

Supporting:

Tianyang Ma, Bochuan Teng, Jinlong Qi, Hailin Zhang, KeWei Wang. Development of high-performance liquid chromatography assay for pharmacokinetic analysis of KCNQ/M-channel opener QO58-lysin in rat plasma [J]. Journal of Chinese Pharmaceutical Sciences, DOI: 10.5246/jcps.2014.03.019.

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Development of high-performance liquid chromatography assay for pharmacokinetic analysis of KCNQ/M-channel opener QO58-lysin in rat plasma

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