An LC-MS/MS method was developed to quantify an antisense oligonucleotide against Raf-1 expression (rafAON) in monkey and mouse plasma and in mouse tissue homogenates from animals dosed with a liposome-entrapped rafAON easy-to-use formulation (LErafAON-ETU) intended for use as an antineoplastic agent. RafAON was extracted from mouse and monkey plasma using solid-phase extraction. Tissues were homogenized and sample cleanup was achieved by protein precipitation. RafAON and the internal standard (IS) were separated on a Hamilton PRP-1 column and quantified by tandem mass spectrometry using an electrospray source in negative ion mode. The total run time was 4.0 min. The peak areas of two rafAON transitions were summed and plotted against the peak area of an IS transition to generate the standard curve. In monkey plasma the linear range was 50-10,000 ng/mL, and in mouse plasma it was 25-5000 ng/mL. The lower limit of quantification was 500 ng/mL (10 microg/g tissue) in heart, kidney, liver, lung and spleen homogenates, and the standard curve was linear up to 10,000 ng/mL. Accuracy, precision and stability were evaluated and found to be acceptable in all three matrices. The assay was used to support pharmacokinetics and tissue distribution studies of LErafAON-ETU in mice and monkeys.
A rapid, specific, and reproducible high-pressure liquid chromatographic method was developed for the determination of cefoperazone concentration in serum and tissue. The assay uses a simple methanol extraction, with cefoxitin as the internal standard. The limits of detection are 1 to 150 ,ug/ml; the maximum coefficient of variation is 7.4%. Using the same chromatography column, ,uBondapak phenyl, and mobile-phase 0.005 M tetrabutylammonium buffer-acetonitrile (80:20), the method can be easily adapted for the analysis of cefoxitin and moxalactam.
Cefoperazone penetration into skeletal muscle and wound drainage in patients undergoing major surgery of the head and neck was measured by high-pressure liquid chromatography. Cefoperazone (2 g) was infused over 30 min before surgery and every 8 h for three postoperative doses. Simultaneous samples of serum and sternomastoid muscle were collected in 18 patients at 135 to 480 min after infusion. Mean cefoperazone concentrations in muscle tissue were 17.1% of those in simultaneously collected serum. Steady-state wound drainage concentrations after the fourth dose of cefoperazone averaged 55.2 Fxg/ml at 1 to 2 h and 62
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