色谱法
化学
活性代谢物
药代动力学
萃取(化学)
特应性皮炎
代谢物
选择性反应监测
人血浆
梯度洗脱
液相色谱-质谱法
基质(化学分析)
串联质谱法
高效液相色谱法
质谱法
药理学
免疫学
医学
生物化学
生物
作者
Jingying Wu,Liang Zheng,Qian Zhang,Qin Zhang,Huiling Qin,Renpeng Zhou,Zhaoxing Chu,Guangwei He,Ling Wang,Wei Hu
摘要
HY072808 is a novel phosphodiesterase 4 inhibitor currently under clinical development to treat atopic dermatitis. The first step is to address the pharmacokinetics and safety after topical administration of HY072808 ointments in healthy humans. In this study, we developed a highly sensitive liquid chromatography-tandem mass spectrometry method to determine plasma HY072808 and its active metabolite, ZZ24, in tiny amounts. The plasma samples were prepared using a simple liquid-liquid extraction method. Liquid chromatographic separation was achieved by gradient elution. The MS/MS quantification was performed in positive ion mode via multiple reaction monitoring. The method showed satisfactory linearity from 10 to 4,000 pg/ml for HY072808 and ZZ24. There was no significant interference from blank plasma. The method was validated for accuracy and precision, matrix effect and extraction recovery, dilution integrity, injection carryover and stability according to the related guidelines of the regulatory authorities. The HY072808 and ZZ24 concentrations in human plasma from a clinical trial were determined using this method. In conclusion, the validated method was robust and could be utilized to support the clinical development of HY072808.
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