School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China; New Drug Research & Development Center, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.
School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jun 1;960:14-8. doi: 10.1016/j.jchromb.2014.04.010. Epub 2014 Apr 13.
DG-7 (11,14-dihydroxy-7,20-epoxy-20-O-derivative of ent-kaurene diterpenoid) is a novel anti-tumor candidate drug. A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of DG-7 in rat plasma. An aliquot of 50 μL plasma sample was prepared by liquid-liquid extraction with ethyl acetate. Chromatographic separation was accomplished on a Waters XTerra C18 column (2.1 mm × 150 mm, 5 μm) with an isocratic elution system consisting of methanol and water. Detection was performed by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode. The optimized fragmentation transitions for MRM were m/z 590.1→m/z 260.0 for DG-7 and m/z 180.3→m/z 110.1 for phenacetin (internal standard). The method was linear over the concentration range of 5-2,500 ng/mL. The intra- and inter-day precisions were less than 7.9% and the accuracy was within ± 9.0%. The mean recovery of DG-7 ranged from 76.8% to 79.2%. The validated method has been successfully applied to a pharmacokinetic study in rats after intravenous administration of DG-7.
DG-7（11,14-二羟基-7,20-环氧-20-O-贝壳杉烯二萜类化合物衍生物）是一种新型的抗肿瘤候选药物。建立并验证了一种灵敏、特异的液相色谱-串联质谱（LC-MS/MS）法，用于测定大鼠血浆中的 DG-7。采用乙酸乙酯进行液液萃取，取 50 μL 血浆样品进行处理。色谱分离在 Waters XTerra C18 柱（2.1mm×150mm，5μm）上进行，采用甲醇-水为流动相的等度洗脱系统。采用电喷雾正离子模式进行多反应监测（MRM）模式检测。MRM 的优化碎裂转换为 m/z 590.1→m/z 260.0（DG-7）和 m/z 180.3→m/z 110.1（内标苯乙酮）。该方法在 5-2500ng/mL 浓度范围内呈线性。日内和日间精密度均小于 7.9%，准确度在±9.0%范围内。DG-7 的平均回收率为 76.8%-79.2%。该验证方法已成功应用于大鼠静脉注射 DG-7 后的药代动力学研究。
