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Development and validation of a novel method for measuring free concentrations of F and NF in plasma are reported here. The plasma filtrate was prepared by a high\u2010speed short\u2010duration ultrafiltration (UF) and then submitted directly to a short\u2010column liquid chromatography\/tandem mass spectrometric (LC\/MS\/MS) assay. There was no significant matrix effect on the analysis, and non\u2010specific binding of the analytes to the UF devices was negligible. For validation of the method, the recovery of the free analytes was compared to that from an optimized equilibrium dialysis method, and analyte stability was examined under conditions mimicking the sample storage, handling, and analysis procedures. The linearity range was 0.37\u201312\u2009ng\/mL for F and NF; the within\u2010run and between\u2010run relative standard deviations were less than 11.9%, and accuracies across the assay range were 100\u2009\u00b1\u200910.3%. This new method was then further validated in a pharmacokinetic (PK) study in beagle dogs receiving a single oral dose of fluoxetine hydrochloride. The integrity of the resulting PK data of free F and NF was absolute. The PK data indicate that the novel method is accurate and reliable. To our knowledge this is the first report describing a rapid and reliable method for direct measurement of free concentrations of F and NF in plasma, which will be useful for clinical pharmacokinetic\/pharmacodynamic studies of F. Furthermore, the strategies described herein may be applied to the development and validation of methods for measuring the free concentrations of other drugs in plasma. Copyright \u00a9 2005 John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/rcm.2265","type":"journal-article","created":{"date-parts":[[2005,11,24]],"date-time":"2005-11-24T13:46:20Z","timestamp":1132839980000},"page":"39-47","source":"Crossref","is-referenced-by-count":35,"title":["Rapid and direct measurement of free concentrations of highly protein\u2010bound fluoxetine and its metabolite norfluoxetine in plasma"],"prefix":"10.1002","volume":"20","author":[{"given":"Bin","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangji","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laishun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,24]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0022-5347(25)00352-0","volume":"241","author":"De Rick AF","year":"1987","journal-title":"J. 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