Mass Spectral Profile for Rapid Differentiating Beta-Lactams from Their Ring-Opened Impurities

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis
• Mass Spectrometry

Background:

• High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) is crucial for determining beta-lactam antibiotics.
• Current HPLC-MS methods are insufficient for identifying impurities in these drugs.
• Impurities can affect drug safety and efficacy.

Purpose of the Study:

• To develop and validate a method for identifying beta-lactam and ring-opened beta-lactam impurities.
• To characterize collision-induced dissociation (CID) spectra of beta-lactam antibiotics and their impurities.
• To apply these spectral characteristics for rapid impurity profiling.

Main Methods:

• Extraction of characteristic CID spectral profiles from HPLC-MS data for six beta-lactam antibiotics and 45 impurities.
• Confirmation of spectral data using literature values.
• Application of spectral characteristics for differentiating impurity types in cefixime, cefdinir, and cefaclor.

Main Results:

• Characteristic CID spectral profiles were obtained under low activating voltage.
• Diagnostic fragmentations were identified for determining double bond and substituent localization.
• Potential fragmentations for differentiating configurations of ring-opened impurities were observed.
• 45 impurities were successfully identified in cefixime, cefdinir, and cefaclor capsules.

Conclusions:

• The developed CID spectral analysis method enables rapid differentiation of beta-lactam and ring-opened beta-lactam impurities.
• This approach enhances the identification of impurities in frequently used beta-lactam antibiotics.
• The method shows promise for characterizing stereochemistry of impurities, a challenge in mass spectrometry.