Quantification of crisugabalin (HSK16149) in biological matrix by LC-MS/ MS method: An application to rat pharmacokinetic and tissue distribution studies

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作   者：

Wang, Zeyu;  Tang, Pingming;  Dou, Caixia;  Shen, Jiale;  Peng, Ni;  Li, Yao;  Wang, Ju;  Chen, Xiaoyan; 

作者机构：

Chinese Acad Sci;  Haisco Pharmaceut Grp Co Ltd; 

关键词：

Crisugabalin (HSK16149);  LC-MS/MS;  Tissue distribution;  Pharmacokinetics; 

期刊名称：

Journal of chromatography,B.Analytical technologies in the biomedical and life sciences

i s s n：

1570-0232

年卷期：

2025 年 1251 卷

页   码：

摘   要：

Crisugabalin (HSK16149), a novel VGCC alpha 2S ligand, has been approved for the treatment of adult diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN). In this study, an LC-MS/MS method was developed for the determination of crisugabalin in rat plasma and tissues homogenate. Samples were extracted by protein precipitation and separated on a Hypersil GOLD aQ column with methanol and 2 mM ammonium acetate in water containing 0.1 % formic acid as mobile phase. Crisugabalin and its internal standard HSK7891 were ionized by electrospray ionization source and detected by multiple reaction monitoring with transitions of m / z 210.9-* 134.4 and m / z 246.0-* 129.3. Over the range of 0.0100-10.0 mu g/mL, the selectivity, linearity, precision and accuracy, matrix effect, stability, recovery and dilution integrity of crisugabalin were validated in rat plasma. Validation was also performed in rat liver homogenate at concentrations ranging from 0.0200-20.0 mu g/g. The method was then successfully applied to determine the pharmacokinetics and tissue distribution of crisugabalin. In rats, orally administered crisugabalin was completely and rapidly absorbed with a peak time of about 0.57 h, and was mainly distributed to kidney, bladder and liver tissues. Crisugabalin exhibited linear pharmacokinetics over the oral dose range of 3-30 mg/kg.