Ji Young Seok, Kim Tae Kon
College of Science and Engineering, Jungwon University, Chungbuk, South Korea.
Biomed Chromatogr. 2020 Apr;34(4):e4749. doi: 10.1002/bmc.4749. Epub 2020 Jan 21.
A sensitive method for quantitation of SK1326 in rat plasma has been established using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI/MS/MS). SK1326 and the internal standard (tramadol) in plasma sample were extracted using acetonitrile. A centrifuged upper layer was then evaporated and reconstituted with a mobile phase of 0.5% formic acid-acetonitrile (35:65, v/v). The reconstituted samples were injected into a C reversed-phase column. Using MS/MS in the multiple reaction monitoring mode, SK1326 and tramadol were detected without severe interference from the rat plasma matrix. SK1326 produced a protonated precursor ion ([M + H] ) at m/z 432.3 and a corresponding product ion at m/z 114.4. The internal standard produced a protonated precursor ion ([M + H] ) at m/z 264.4 and a corresponding product ion at m/z 58.1. Detection of SK1326 in rat plasma by the UPLC-ESI/MS/MS method was accurate and precise with a quantitation limit of 1.0 ng/mL. The validation, reproducibility, stability and recovery of the method were evaluated. The method has been successfully applied to pharmacokinetic studies of SK1326 in rat plasma. The pharmacokinetic parameters of SK1326 were evaluated after intravenous (at a dose of 10 mg/kg) and oral (at a dose of 20 mg/kg) administration of SK1326 in rats. After oral administration (20 mg/kg) of SK1326, the F (fraction absorbed) value was ~77.1%.
采用超高效液相色谱 - 电喷雾电离串联质谱法（UPLC - ESI/MS/MS）建立了一种灵敏的大鼠血浆中SK1326定量分析方法。血浆样品中的SK1326和内标（曲马多）用乙腈萃取。然后将离心后的上层清液蒸发，并用0.5%甲酸 - 乙腈（35:65，v/v）的流动相复溶。复溶后的样品注入C反相柱。在多反应监测模式下采用MS/MS，SK1326和曲马多的检测不受大鼠血浆基质的严重干扰。SK1326在m/z 432.3处产生质子化前体离子（[M + H]），在m/z 114.4处产生相应的产物离子。内标在m/z 264.4处产生质子化前体离子（[M + H]），在m/z 58.1处产生相应的产物离子。采用UPLC - ESI/MS/MS法检测大鼠血浆中的SK1326准确、精密，定量限为1.0 ng/mL。对该方法的验证、重现性、稳定性和回收率进行了评估。该方法已成功应用于大鼠血浆中SK1326的药代动力学研究。在大鼠静脉注射（剂量为10 mg/kg）和口服（剂量为20 mg/kg）SK1326后，评估了SK1326的药代动力学参数。口服SK1326（20 mg/kg）后，F（吸收分数）值约为77.1%。
