title: 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.
abstract: 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.
authors.affiliation: Bioanalytical Research Department, Veeda Clinical Research, Ambawadi, Ahmedabad 3800015, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Yadav
authors.forename: Dharmesh
authors.initials: D
authors.lastname: Patel
authors.forename: Puran
authors.initials: P
authors.lastname: Singhal
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
authors.forename: Sailendra
authors.initials: S
authors.lastname: Goswami
authors.forename: Pranav S
authors.initials: PS
authors.lastname: Shrivastav
authors.forename: Umesh C
authors.initials: UC
authors.lastname: Pande
mesh_terms: D016477:Artifacts; D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004176:Dipyridamole / Q000097:blood*; D005740:Gases / Q000097:blood; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D005740:Gases; D004176:Dipyridamole