Pharmacokinetics and tissue distribution study of novel potent antiplatelet agent S007-867 in mice using HPLC-MS/MS

• Published in: Xenobiotica Vol. 45; no. 6; pp. 530 - 537
• Main Authors: Chandasana, Hardik, Chhonker, Yashpal S., Prasad, Yarra Durga, Laxman, Tulsankar Sachin, Anil Kumar, K. S., Dikshit, Dinesh K., Bhatta, Rabi S.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.06.2015; Informa Healthcare
• Subjects: Animals; Antithrombotic; Chromatography, High Pressure Liquid; Female; LC-MS/MS; Male; Mass Spectrometry; Mice; Organ Specificity - drug effects; pharmacokinetics; Platelet Aggregation Inhibitors - pharmacokinetics; Platelet Aggregation Inhibitors - pharmacology; tissue distribution; validation; pharmacokinetics; LC-MS/MS; validation; Antithrombotic; tissue distribution
• ISSN: 0049-8254; 1366-5928
• DOI: 10.3109/00498254.2014.994053

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.