title: Pharmacokinetics and tissue distribution study of novel potent antiplatelet agent S007-867 in mice using HPLC-MS/MS.
abstract: 1. S007-867 is a novel antiplatelet agent that shows promising in vitro and in vivo efficacy. For further development and better pharmacological elucidation, we characterized pharmacokinetics and tissue distribution of S007-867 in a mouse model. 2. A sensitive, selective and robust LC-MS/MS method was developed and validated in the mouse plasma and tissue for quantification of S007-867. The chromatographic separation was performed on Waters Symmetry Shield C18 column (150 × 4.6 mm, 5 µm) using methanol and ammonium acetate buffer. 3. S007-867 was rapidly absorbed and distributed to various tissues. Following single oral administration of S007-867 in the mouse, the concentration was in the order of C intestine > C liver > C kidney > C heart > C spleen > C lungs > C brain. Tissue to plasma area under the plasma curve ratio suggested that the maximum amount of drug was found in the intestine and liver. Half life of S007-867 was found longer in the heart (8.08 h), spleen (∼ 7.94 h) and kidney (∼ 15.41 h) as compared with other tissues. 4. The preclinical pharmacokinetics and tissue distribution data obtained using this LC-MS/MS method are expected to assist the future clinical investigations of S007-867 as a promising antiplatelet agent.
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR - Central Drug Research Institute , Lucknow, Uttar Pradesh , India .
authors.forename: Hardik
authors.initials: H
authors.lastname: Chandasana
authors.forename: Yashpal S
authors.initials: YS
authors.lastname: Chhonker
authors.forename: Yarra Durga
authors.initials: YD
authors.lastname: Prasad
authors.forename: Tulsankar Sachin
authors.initials: TS
authors.lastname: Laxman
authors.forename: K S
authors.initials: KS
authors.lastname: Anil Kumar
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Dikshit
authors.forename: Rabi S
authors.initials: RS
authors.lastname: Bhatta
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D009928:Organ Specificity / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors
keywords: Antithrombotic; LC-MS/MS; pharmacokinetics; tissue distribution; validation