title: Development and validation of a rapid method for the detection of latrunculol A in plasma.
abstract: Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged at 14,000 rpm at 4 °C for 25 min. The supernatant was injected in an HPLC system comprising a Waters Symmetry NH(2) column, a mobile phase of acetonitrile/water (95/5, v/v), a flow rate of 1.0 mL/min, at 220 nm. The method was validated by parameters including a good linear correlation, a limit of quantification of 9 ng/mL, and a good precision with a coefficient variation of 1.65, 1.86, and 1.26% for 20, 400, and 800 ng/mL, respectively. With this simple method, excellent separation and sensitivity of latrunculol A are achieved, thus allowing a rapid analysis of the plasma samples for absorption, distribution, and metabolism studies.
authors.affiliation: Henry Ford Health System, Detroit, MI 48202, USA. jiajiushaw@gmail.com
authors.forename: Jiajiu
authors.initials: J
authors.lastname: Shaw
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Valeriote
authors.forename: Joseph
authors.initials: J
authors.lastname: Media
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Johnson
authors.forename: Taro
authors.initials: T
authors.lastname: Amagata
authors.forename: Karen
authors.initials: K
authors.lastname: Tenney
authors.forename: Phillip
authors.initials: P
authors.lastname: Crews
mesh_terms: D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D005260:Female; D018942:Macrolides / Q000097:blood* / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D053778:Thiazolidines / Q000097:blood* / Q000737:chemistry; D013997:Time Factors
chemical_list: D018942:Macrolides; D053778:Thiazolidines; C555732:latrunculol A