Characterization of novel hydrolysis products of carbapenems by electrospray ionization mass spectrometry.
Carbapenems, including meropenem and imipenem, exhibit low stability against acid or base reagents. The fragmentation behavior of meropenem and its acid hydrolysis products was investigated by Fourier transform ion cyclotron resonance electrospray ionization tandem mass spectrometry and ion trap tandem multi-stage mass spectrometry in both positive and negative ion mode. Only one neutral loss of CO(2) was observed from the precursor ion to the MS(4) product ions for the acid hydrolysis product and this behavior did not correspond to that expected for the previously accepted 1-pyrroline or 2-pyrroline structure with two carbonyl acid units. The unknown product was then proposed to be 2-(4-(5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-5-imino-3-methyl-6-oxotetrahydro-2H-pyran-2-yl)-3-hydroxybutanoic acid on the basis of the multi-stage mass spectrometric and accurate mass data. A similar acid hydrolysis product of imipenem was also identified by mass spectrometry, confirming that these carbapenems had the same acid hydrolysis behavior. The proposed structures were further confirmed by NMR experiments.
Sun
Cuirong
C
Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
Wu
Jianmei
J
Pan
Yuanjiang
Y
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D015780:Carbapenems / Q000737:chemistry*; D006868:Hydrolysis; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000900:Anti-Bacterial Agents; D015780:Carbapenems