title: Simultaneous quantification of cilostazol and its primary metabolite 3,4-dehydrocilostazol in human plasma by rapid liquid chromatography/tandem mass spectrometry.
abstract: A simple, rapid, sensitive and selective liquid chromatography/electrospray tandem mass spectrometry method was developed and validated for the simultaneous quantification of cilostazol and its primary metabolite 3,4-dehydrocilostazol in human plasma using mosapride as an internal standard. The method involves a simple one-step liquid-liquid extraction with a diethyl ether and dichloromethane mixture (7:3). The analytes were chromatographed using an isocratic mobile phase on a reversed-phase C18 column and analyzed by mass spectrometry in the multiple reaction monitoring mode using the respective [M+H]+ ions, m/z 370/288 for cilostazol, m/z 368/286 for 3,4-dehydrocilostazol and m/z 422/198 for the internal standard. The assay exhibited a linear dynamic range of 5-2,000 ng/mL for cilostazol and 5-400 ng/mL for 3,4-dehydrocilostazol in human plasma. The lower limit of quantitation was 5 ng/mL for both cilostazol and its metabolite. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. A run time of 2.5 min for each sample made it possible to analyze more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetics, bioavailability or bioequivalence studies.
authors.affiliation: Biopharmaceutical Research, Suven Life Sciences Ltd., Serene Chambers, Road no. 7, Banjara Hills, Hyderabad, 500034, India. ramakrishna_nirogi@yahoo.co.in
authors.forename: Ramakrishna V S
authors.initials: RV
authors.lastname: Nirogi
authors.forename: Vishwottam N
authors.initials: VN
authors.lastname: Kandikere
authors.forename: Manoj
authors.initials: M
authors.lastname: Shukla
authors.forename: Koteshwara
authors.initials: K
authors.lastname: Mudigonda
authors.forename: Wishu
authors.initials: W
authors.lastname: Shrivasthava
authors.forename: Praveen V
authors.initials: PV
authors.lastname: Datla
authors.forename: Anjaneyulu
authors.initials: A
authors.lastname: Yerramilli
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D000077407:Cilostazol; D006801:Humans; D015394:Molecular Structure; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013777:Tetrazoles / Q000097:blood*; D013997:Time Factors
chemical_list: D013777:Tetrazoles; C519131:3,4-dehydrocilostazol; D000077407:Cilostazol