Yuan-Qing Xia1, Eugene Ciccimaro2, Naiyu Zheng3, Mingshe Zhu2. 1. Application Support North America, Sciex, 500 Old Connecticut Path, Framingham, MA 01701, USA. 2. Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA. 3. Analytical & Bioanalytical Operations, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
Abstract
AIM: It is challenging to develop a multiple reaction monitoring (MRM) method for some disulfide-bonded peptides with inefficient collision-induced dissociation fragmentation. This study describes a new methodology using differential mobility spectrometry (DMS) combined with multiple ion monitoring (MIM) to enhance bioanalytical sensitivity for sunflower trypsin inhibitor. RESULTS: By combining DMS with MIM to monitor the intact precursor ion in Q1 and Q3 MS analyzers, a lower limit of quantitation at 0.125 ng/ml was achieved to quantify sunflower trypsin inhibitor in rat plasma, representing a 40-fold sensitivity improvement over MIM without DMS. CONCLUSION: DMS coupled with MIM method provides triple quadrupole MS users an effective means to overcome challenges in analyzing disulfide-bonded peptides or other analytes that do not have useful collision-induced dissociation fragment ions for MRM analysis.
AIM: It is challenging to develop a multiple reaction monitoring (MRM) method for some disulfide-bonded peptides with inefficient collision-induced dissociation fragmentation. This study describes a new methodology using differential mobility spectrometry (DMS) combined with multiple ion monitoring (MIM) to enhance bioanalytical sensitivity for sunflower trypsin inhibitor. RESULTS: By combining DMS with MIM to monitor the intact precursor ion in Q1 and Q3 MS analyzers, a lower limit of quantitation at 0.125 ng/ml was achieved to quantify sunflower trypsin inhibitor in rat plasma, representing a 40-fold sensitivity improvement over MIM without DMS. CONCLUSION: DMS coupled with MIM method provides triple quadrupole MS users an effective means to overcome challenges in analyzing disulfide-bonded peptides or other analytes that do not have useful collision-induced dissociation fragment ions for MRM analysis.
Entities:
Keywords:
differential mobility spectrometry; disulfide-bonded peptides; multiple ion monitoring