Chaiyasaeng Worawut, Hongwiset Darunee, Tocharus Chainarong, Punyawudho Baralee, Tocharus Jiraporn, Chaichompoo Waraluck, Rojsitthisak Pornchai, Pabuprapap Wachirachai, Yingyongnarongkul Boon-Ek, Suksamrarn Apichart
Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkapi, Bangkok 10240, Thailand.
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
ACS Omega. 2024 Sep 19;9(39):41032-41042. doi: 10.1021/acsomega.4c06604. eCollection 2024 Oct 1.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine hexahydrocurcumin (HHC) levels in mouse plasma, brain, liver, and kidneys using a negative ion mode electrospray ionization (ESI) source. Demonstrating a lower limit of quantification (LLOQ) of 5 ng/mL, the method showed excellent linearity across a concentration range of 5-500 ng/mL in all tested matrices. Precision evaluations reported a coefficient of variation (CV%) of less than 13.19% for both intraday and interday measurements, while accuracy ranged from 95.13 to 105.07% across all quality control levels. HHC extraction recovery was consistently observed between 70.18 and 93.28%, with a CV% deviation of less than 15%. In the pharmacokinetic evaluation of HHC in mice following a single intraperitoneal (IP) or oral administration, a noncompartment analysis was utilized. After IP administration (40 mg/kg), the value was 47.90 times higher than that achieved via oral administration. Peak plasma concentrations were observed approximately 5 min post-IP and 15 min post-oral dosing. The observed half-lives after these administrations were approximately 1.52 and 2.17 h for IP and oral routes, respectively. Oral administration revealed a relative bioavailability of only 12.28% compared with the IP route. Furthermore, following IP administration, the half-life values in brain, liver, and kidney were not significantly different but more than the half-life value found in plasma. The liver and kidney exhibited the highest concentrations of HHC, while the brain showed the least, suggesting that the hydrophobic nature of HHC impedes its passage through the blood-brain barrier. This study is the first to provide detailed insights into the pharmacokinetics and tissue distribution characteristics of HHC following oral and IP administration in mice, setting the stage for further focus on HHC as a potential new drug candidate.
建立并验证了一种液相色谱-串联质谱（LC-MS/MS）方法，用于使用负离子模式电喷雾电离（ESI）源测定小鼠血浆、脑、肝和肾中的六氢姜黄素（HHC）水平。该方法的定量下限（LLOQ）为5 ng/mL，在所有测试基质中，在5-500 ng/mL的浓度范围内显示出良好的线性。精密度评估报告，日内和日间测量的变异系数（CV%）均小于13.19%，而在所有质量控制水平下，准确度范围为95.13%至105.07%。HHC的提取回收率始终在70.18%至93.28%之间，CV%偏差小于15%。在单次腹腔注射（IP）或口服给药后对小鼠进行的HHC药代动力学评估中，采用了非房室分析。腹腔注射（40 mg/kg）后，AUC值比口服给药高47.90倍。腹腔注射后约5分钟和口服给药后15分钟观察到血浆峰值浓度。这些给药后的观察到的半衰期，腹腔注射和口服途径分别约为1.52小时和2.17小时。与腹腔注射途径相比，口服给药的相对生物利用度仅为12.28%。此外，腹腔注射后，脑、肝和肾中的半衰期值无显著差异，但高于血浆中的半衰期值。肝和肾中HHC的浓度最高，而脑中的浓度最低，这表明HHC的疏水性阻碍了其通过血脑屏障。本研究首次详细深入地研究了小鼠口服和腹腔注射后HHC的药代动力学和组织分布特征，为进一步将HHC作为潜在的新药候选物奠定了基础。
