Kim Nam Jin, Oh Sei-Ryang, Lee Hyung Kyu, Lee Hye Suk
Wonkwang University, Iksan, Republic of Korea.
J Pharm Biomed Anal. 2009 Aug 15;50(1):53-7. doi: 10.1016/j.jpba.2009.03.036. Epub 2009 Apr 7.
A purified extract isolated from the dried flower buds of Magnolia fargesii (NDC-052) is currently being evaluated for phase III clinical trials as a new anti-asthma drug. A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for the simultaneous determination of magnolin and epimagnolin A, the major bioactive components of NDC-052, in rat plasma was developed. After liquid-liquid extraction with tolterodine as an internal standard, magnolin and epimagnolin A were separated on a Luna phenyl-hexyl column with the mobile phase of 70% methanol in 10mM ammonium formate. The analytes were detected by an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curves were linear over the concentration range of 50-2500ng/mL for magnolin and epimagnolin A in rat plasma. The intra- and inter-day coefficients of variation and relative errors for magnolin and epimagnolin A at four QC concentrations were 1.5-11.4% and 5.9-12.5%, respectively. The lower limits of quantification for magnolin and epimagnolin A were 50.0ng/mL using 50microL of plasma. This method was successfully applied to the pharmacokinetic study of magnolin and epimagnolin A after an oral administration of NDC-052 in male Sprague-Dawley rats.
一种从望春玉兰干燥花蕾中分离得到的纯化提取物(NDC - 052)目前正作为一种新型抗哮喘药物进行III期临床试验评估。建立了一种快速、灵敏且选择性好的液相色谱 - 串联质谱(LC/MS/MS)法,用于同时测定大鼠血浆中NDC - 052的主要生物活性成分厚朴酚和表厚朴酚A。以托特罗定作为内标进行液 - 液萃取后,厚朴酚和表厚朴酚A在Luna苯基己基柱上分离,流动相为含10mM甲酸铵的70%甲醇。通过电喷雾电离串联质谱在多反应监测模式下检测分析物。大鼠血浆中厚朴酚和表厚朴酚A的标准曲线在50 - 2500ng/mL浓度范围内呈线性。在四个质量控制浓度下,厚朴酚和表厚朴酚A的日内和日间变异系数及相对误差分别为1.5 - 11.4%和5.9 - 12.5%。使用50μL血浆时,厚朴酚和表厚朴酚A的定量下限为50.0ng/mL。该方法成功应用于雄性Sprague - Dawley大鼠口服NDC - 052后厚朴酚和表厚朴酚A的药代动力学研究。