title: Simultaneous determination of lidamycin enediyne chromophore (LDC) and its aromatized derivative (LDCA) using puerarin as internal standard in rat plasma by LC-MS/MS.
abstract: Lidamycin (LDM), a promising enediyne antitumor antibiotic, was quantified by detecting lidamycin enediyne chromophore (LDC) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the first time. A simple, rapid and reliable method was developed and validated to determine LDC and its aromatized derivative (LDCA) simultaneously in plasma. Puerarin was used as an internal standard (IS), and plasma samples were pretreated with one-step precipitation by acetonitrile. Separation was achieved on a reverse-phase C(18) column with a mobile phase composed of methanol and water containing 5 mm ammonium acetate at pH 3.5 in gradient elution mode. Detection was performed on a triple quadrupole tandem mass spectrometer using electrospray ionization (ESI) by multiple reaction monitoring (MRM) in the negative ion mode. Good linearity was obtained over the concentration range of 0.2-100 µg/mL for LDM. Precision and accuracy were validated by RSD% values in the range of 2.6-13.0% and RE% values between -4.6 and 3.8%, respectively. In addition, no specificity and matrix effects were observed. The recovery was found to be 99.2-111.0% and stability in various conditions was found to be acceptable. This method was applied in preclinical pharmacokinetic studies for routine monitoring of LDM in rat plasma.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Blood Transfusion Medical Science, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Wen
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Chen
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Meng
authors.forename: Hui
authors.initials: H
authors.lastname: Gan
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zhu
authors.forename: Zhuona
authors.initials: Z
authors.lastname: Wu
authors.forename: Ruolan
authors.initials: R
authors.lastname: Gu
authors.forename: Guifang
authors.initials: G
authors.lastname: Dou
mesh_terms: D000617:Aminoglycosides / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D053281:Enediynes / Q000097:blood* / Q000493:pharmacokinetics; D006207:Half-Life; D007529:Isoflavones / Q000097:blood* / Q000493:pharmacokinetics; D057230:Limit of Detection; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D000617:Aminoglycosides; D053281:Enediynes; D007529:Isoflavones; C058024:C 1027; C033607:puerarin