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Effect of collision‐activated dissociation gas and collision energy on the fragmentation of dipyridamole and its rapid and sensitive liquid chromatography/electrospray ionization tandem mass spectrometric determination in human plasma
Author(s) -
Yadav Manish,
Patel Dharmesh,
Singhal Puran,
Prasad Rajendra,
Goswami Sailendra,
Shrivastav Pranav S.,
Pande Umesh C.
Publication year - 2008
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.3383
Subject(s) - chemistry , fragmentation (computing) , collision induced dissociation , dissociation (chemistry) , electrospray , tandem mass spectrometry , chromatography , electrospray ionization , collision , tandem , ionization , analytical chemistry (journal) , mass spectrometry , plasma , ion , organic chemistry , nuclear physics , computer science , operating system , materials science , physics , computer security , composite material
The effect of nitrogen as the collision‐activated dissociation (CAD) gas on the fragmentation of dipyridamole was investigated in the range of 10–90 eV collision energy. The results support the collision model reported elsewhere, that the degree of ion fragmentation increases with the increasing mass of the collision gas. A simple, sensitive and high‐throughput liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed for the determination of dipyridamole, a platelet aggregation inhibitor in human plasma, using granisetron as internal standard (IS). The method involved liquid–liquid extraction of the analyte and IS from 0.5 mL human plasma with diethyl ether. The chromatographic separation was achieved under isocratic conditions and the ion transitions for dipyridamole ( m/z 505.40 → 429.60) and the IS ( m/z 313.10 → 138.20) were monitored on a triple quadrupole mass spectrometer, operating in positive ion multiple reaction monitoring (MRM) mode. The method was validated over the concentration range 5.1–4499.1 ng/mL for dipyridamole. The method was rugged and rapid with a total run time of 1.2 min. It was successfully applied to a pivotal bioequivalence study in 67 healthy human subjects after oral administration of a 75 mg extended release formulation under fasting condition. Copyright © 2008 John Wiley & Sons, Ltd.