title: Simultaneous determination of 7-O-succinyl macrolactin A and its metabolite macrolactin A in rat plasma using liquid chromatography coupled to tandem mass spectrometry.
abstract: 7-O-Succinyl macrolactin A (SMA) and its major metabolite macrolactin A (MA) are generated from Bacillus polyfermenticus KJS-2. Both substances show inhibitory effects on angiogenesis and cancer cell invasion. SMA in rat plasma is known to be relatively stable at room temperature, but MA was not detected due to its instability. Therefore, a stabilizer is required to accurately measure the substance in biological rat samples. In this study, NaF and eserine were examined to determine whether they could stabilize MA to allow for accurate measurement in rat plasma. We also developed a rapid and simple chromatographic method using tandem mass spectrometry (MS/MS) for the simultaneous determination of these compounds in rat plasma. After simple protein precipitation with acetonitrile including methaqualone (internal standard), the analytes were chromatographed on a Hilic column with a mobile phase of 10mM formic acid aqueous solution, methanol, and acetonitrile (15:15:70, v/v). The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This analytical method was successfully applied to monitor plasma concentrations of both compounds over time following intravenous administration of a salt form of SMA in rats.
authors.affiliation: College of Pharmacy, Yeungnam University, Kyoungbuk 712-749, South Korea.
authors.forename: Keumhan
authors.initials: K
authors.lastname: Noh
authors.affiliation: Research and Development Center, Daewoo Pharm. Co. Ltd., Busan 604-836, South Korea.
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Kyoungbuk 712-702, South Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea.
authors.forename: Hwi-yeol
authors.initials: HY
authors.lastname: Yun
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756, South Korea. Electronic address: eykimjcb777@cau.ac.kr.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756, South Korea. Electronic address: wkang@cau.ac.kr.
authors.forename: Wonku
authors.initials: W
authors.lastname: Kang
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D004355:Drug Stability; D018942:Macrolides / Q000097:blood* / Q000737:chemistry*; D010949:Plasma / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: C559723:7-O-succinyl macrolactin A; D018942:Macrolides; C453562:macrolactin A
keywords: 7-O-Succinyl macrolactin A; LC–MS/MS; Macrolactin A; Rat plasma; Stability