College of Pharmaceutical Sciences & College of Chinese Medicine, Southwest University, Chongqing 400715, China.
J Pharm Biomed Anal. 2012 Nov;70:337-43. doi: 10.1016/j.jpba.2012.05.016. Epub 2012 May 28.
Catalpol is a Chinese herb ingredient with potential for the treatment of neurodegenerative disorders. A high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (HPLC-APCI-MS/MS) method was developed and validated to investigate the pharmacokinetics and biodistribution of catalpol in both the plasma and cerebrospinal fluid (CSF) of rats. Methanol was used to precipitate the protein from the biosamples, and the supernatant was collected for the assay. A Diamonsil C18 column (150 mm × 4.6 mm, 5 μm) with a mobile phase of methanol-ammonium acetate (20 mM) (50:50, v/v), a 0.6 mL/min flow rate and a total run time of 3 min was used to separate catalpol and aucubin (internal standard, IS). A triple-quadrupole tandem mass spectrometer with an atmospheric pressure chemical ionization (APCI) source in the positive ion mode was operated in the multiple reaction-monitoring (MRM) mode to determine the concentration of catalpol at m/z 380.0-165.0 and that of IS at m/z 364.0-148.9. The linear range was 10-50000 ng/mL for plasma samples and 20-5000 ng/mL for CSF samples. At both the lower limit of quantification (LLOQ) and three levels QC (quality control) concentrations, the RSD was less than 12.9%, and the bias was -10.0% to 7.1%. The extraction recoveries for catalpol ranged from 72.9% to 109.5% from both rat plasma and CSF. The catalpol was administered to rats in 6 mg/kg doses via intravenous (i.v.) injection, and the pharmacokinetics and biodistribution studies were performed in both plasma and CSF. The results demonstrated that catalpol could be transported into the CSF via the AUC(CSF)/AUC(plasma) of 5.8% with a half-life (t(1/2)) of 1.5 h. Overall, the established HPLC-APCI-MS/MS method is rapid and sensitive, and has been successfully used to quantify catalpol in both plasma and CSF.
梓醇是一种具有治疗神经退行性疾病潜力的中药成分。建立并验证了一种高效液相色谱-大气压化学电离-串联质谱（HPLC-APCI-MS/MS）法，用于研究梓醇在大鼠血浆和脑脊液（CSF）中的药代动力学和生物分布。采用甲醇沉淀生物样品中的蛋白质，收集上清液进行测定。采用 Diamonsil C18 柱（150mm×4.6mm，5μm），以甲醇-乙酸铵（20mM）（50:50，v/v）为流动相，流速为 0.6mL/min，总运行时间为 3min，分离梓醇和京尼平苷酸（内标，IS）。三重四极杆串联质谱仪在正离子模式下采用大气压化学电离（APCI）源，在多重反应监测（MRM）模式下测定梓醇的浓度为 m/z 380.0-165.0，IS 的浓度为 m/z 364.0-148.9。血浆样品的线性范围为 10-50000ng/mL，CSF 样品的线性范围为 20-5000ng/mL。在定量下限（LLOQ）和三个 QC（质量控制）浓度下，RSD 小于 12.9%，偏差为-10.0%至 7.1%。梓醇在大鼠血浆和 CSF 中的提取回收率为 72.9%-109.5%。以 6mg/kg 剂量静脉（i.v.）注射给予大鼠梓醇，并在血浆和 CSF 中进行药代动力学和生物分布研究。结果表明，梓醇可通过 AUC（CSF）/AUC（血浆）的 5.8%进入 CSF，半衰期（t（1/2））为 1.5h。总之，建立的 HPLC-APCI-MS/MS 方法快速灵敏，已成功用于定量测定血浆和 CSF 中的梓醇。
