Determination and pharmacokinetic study of the novel anti-tumor candidate drug DG-7 in rat plasma by liquid chromatography-tandem mass spectrometry.
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.
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.
Juan
J
Li
School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.
Dan-Dan
DD
Liu
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.
Yu
Y
Ke
School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.
Fei
F
Guo
School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.
Xiao-Ming
XM
Ding
School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.
Shuai-Liang
SL
Wang
School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.
Yu
Y
Chen
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. Electronic address: liuhm@zzu.edu.cn.
Hong-Min
HM
Liu
School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.
Ying-Qian
YQ
Su
School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.
Yan-Yang
YY
Nan
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D057230:Limit of Detection; D016014:Linear Models; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000970:Antineoplastic Agents
Anti-tumor; DG-7; LC–MS/MS; Pharmacokinetics; Rat plasma