Determination of three major components of bitespiramycin and their major active metabolites in rat plasma by liquid chromatography-ion trap mass spectrometry.
The rapid, selective and sensitive liquid chromatographic-ion trap mass spectrometric (LC-MS(n)) method was developed and validated for determination of three major components (isovaleryspiramycins, ISV-SPMs) of a novel macrolide antibiotic bitespiramycin and their major active metabolites (spiramycins, SPMs) in rat plasma. The analytes ISV-SPMs, SPMs, internal standard roxithromycin and azithromycin were extracted from plasma samples by liquid-liquid extraction, and chromatographed on a C(18) column using two mobile phase systems. Detection was carried out on an ion trap mass spectrometer by selected reaction monitoring (SRM) mode via electrospray ionization (ESI). Three components (ISV-SPM I, II, III or SPM I, II, III) could be simultaneously determined within 6.5 min. Linear calibration curves were obtained in the concentration ranges of 4-200 ng/ml for ISV-SPM I and SPM I, 12-600 ng/ml for ISV-SPM II and SPM II, and 18-900 ng/ml for ISV-SPM III and SPM III. The intra- and inter-run precision (RSD), calculated from quality control (QC) samples were less than 8.8 and 10.4% for ISV-SPMs, and 9.3 and 11.2% for SPMs, respectively. The method was applied for the evaluation of the pharmacokinetics of bitespiramycin in rats following peroral/intravenous administration.
Zhong
Dafang
D
Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. zhongdf@china.com
Shi
Xiangguo
X
Sun
Lu
L
Chen
Xiaoyan
X
D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D015572:Spiramycin / Q000097:blood* / Q000493:pharmacokinetics
D000890:Anti-Infective Agents; D015572:Spiramycin