title: Validation and implementation of a method for determination of bryostatin 1 in human plasma by using liquid chromatography/tandem mass spectrometry.
abstract: A new sensitive and specific method using liquid chromatography/tandem mass spectrometry for determination of bryostatin 1 was developed and validated. Sample pretreatment involved a double liquid-liquid extraction step with a mixture of acetonitrile/n-butyl chloride (1/4, v/v). Separation of the compound of interest, including the internal standard paclitaxel, was achieved on a Waters X-Terra C18 (50 x 2.1 mm i.d., 3.5 microm) analytical column with acetonitrile/water mobile phase (80:20, v/v) containing 0.1% formic acid using isocratic flow at 0.15 mL/min for 13 min. The analytes of interest were monitored by tandem mass spectrometry with electrospray positive ionization. The linear calibration curves were generated over the range of 50-2000 pg/mL with values for the coefficient of determination of >0.99. The values for both within-day and between-day precision and accuracy were <15%. This method was used to characterize the plasma pharmacokinetics of bryostatin 1 at doses of 20 microg/m2) to optimize treatment with this agent.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Rudek
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Smith
authors.forename: Sharyn D
authors.initials: SD
authors.lastname: Baker
mesh_terms: D054713:Bryostatins; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D016903:Drug Monitoring / Q000379:methods*; D018942:Macrolides / Q000097:blood* / Q000493:pharmacokinetics; D008722:Methods; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods* / Q000592:standards
chemical_list: D054713:Bryostatins; D018942:Macrolides; C046785:bryostatin 1