LC-MS-MS Analysis of Brodifacoum Isomers in Rat Tissue.

Brodifacoum (BDF) is a second-generation anticoagulant rodenticide structurally related to warfarin but containing two chiral centers. Highly stable, BDF can contaminate food and water supplies causing accidental poisoning of humans and nontarget animals. To determine the distribution of BDF isomers in serum and tissues, a quantitative method was developed and validated according to FDA guidelines based on high-performance liquid chromatography-tandem mass spectrometry. A single liquid-liquid extraction step provided recoveries exceeding 93%. Reversed-phase chromatographic separations required <6 min, and quantitative analysis utilized a triple-quadrupole mass spectrometer equipped with negative ion electrospray and selected reaction monitoring. The standard curve had a linear regression coefficient of 0.999 and intra- and inter-assay variations of <10%. The chromatographic method enabled the resolution and measurement of pairs of BDF diastereomers in commercial materials as well as in rat tissues. This method is suitable for measuring BDF exposure as well as basic science studies of the distribution and elimination of BDF diastereomers to various tissues.

Determination of bisphenol A-glucuronide in human urine using ultrahigh-pressure liquid chromatography/tandem mass spectrometry.

RATIONALE: Used widely as a plasticizer and as a monomer for plastics, bisphenol A (BPA) is under investigation as a possible endocrine disrupter. As an indication of systemic exposure, a fast and accurate assay was developed for the major BPA metabolite in human urine, BPA-monoglucuronide (BPA-G), using ultrahigh-pressure liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS). METHODS: Urine samples were prepared using solid-phase mixed-mode reversed-phase/anion-exchange extraction. BPA-G was measured using UHPLC/MS/MS with an amide UHPLC column interfaced to a triple-quadrupole mass spectrometer equipped with negative ion electrospray, collision-induced dissociation and selected reaction monitoring. [(13) C12 ]-BPA-G was used as a surrogate standard. RESULTS: By measuring the glucuronide metabolite of BPA, potential interference due to BPA contamination from containers, solvents, pipette, etc., was avoided. The standard curve had a linear regression coefficient of 0.999, and the intra- and inter-assay variations were less than 10%. The assay was validated according to FDA guidelines. CONCLUSIONS: A fast, accurate, and highly selective method for the determination of BPA-G in human urine was developed and validated using UHPLC/MS/MS. This method is suitable for assessing human exposure to BPA. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model.

PURPOSE: Use of oral sorafenib, an antiangiogenic chemotherapeutic agent for hepatocellular carcinoma (HCC), is limited by an unfavorable side effect profile. Transarterial chemoembolization (TACE) employs targeted intravascular drug administration, and has potential as a novel sorafenib delivery method to increase tumoral concentrations and reduce systemic levels. This study aimed to discern the pharmacokinetics of sorafenib TACE in a rabbit VX2 liver tumor model. METHODS: A 3 mg/kg dose of sorafenib ethiodized oil emulsion was delivered via an arterial catheter to VX2 liver tumors in seven New Zealand white rabbits. Following TACE, serum sorafenib levels were measured at days 0, 1, 2, 3, 7, 10, and 14 until the time of sacrifice, after which rabbit livers were harvested for analysis of sorafenib concentrations within treated tumors and normal liver. Liquid chromatography tandem mass spectrometry was used for drug quantification. RESULTS: Sorafenib uptake within liver tumor and nontumorous liver tissue peaked at mean 3.53 and 0.75 µg/mL, respectively, immediately post-procedure (5:1 tumor to normal tissue drug uptake ratio), before decreasing with a 10-18 hour half-life. Serum sorafenib levels peaked immediately after TACE at a mean value of 58.58 µg/mL before normalizing with a 5.2-hour half-life, suggesting early drug washout from liver into the systemic circulation. Hepatic lab parameters showed transient increase 24 hours post-TACE with subsequent resolution. CONCLUSION: While targeted transarterial delivery of sorafenib ethiodized oil emulsion shows preferential tumor uptake compared to normal liver, systemic washout occurs with a short half-life, resulting in high circulating drug levels.