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A novel method has been developed for the rapid solid phase extraction of drugs and metabolites from biological fluids, prior to further analysis. The newly designed, 96-tube micropreparation block facilitates high throughput by enabling the extraction of 96 samples simultaneously. The system is described, linked to HPLC/APCI-MS/MS, for the determination of darifenacin in human plasma. The resulting procedure, using deuterated darifenacin as internal standard, is validated over the concentration range 25-2000 pg/mliter; accuracy (0.6-4.6%) and precision (3.6-18.8%) are considered acceptable and overall recovery was determined to be approximately 50%.

Mean peak concentrations of fluconazole in plasma and vaginal secretions of females after a 150-mg single oral dose were shown to be 2.82 ,g/ml and 2.43 ,g/g, respectively. Our results indicate that clinically efficacious concentrations of fluconazole in vaginal secretions are easily achieved after this single oral dose.Fluconazole is a new bis-triazole antifungal agent which has shown excellent activity against candidiasis both in animal models and in patients with oropharyngeal or vaginal candidiasis (1, 3, 4). As well as having good absorption after oral administration (>90% bioavailability), a long plasma half-life (25 h), and low protein binding (12%), fluoconazole is rapidly distributed in body tissue fluids (2). The activity of fluoconazole against oropharyngeal candidiasis has been partially attributed to its presence in saliva, where levels of magnitude similar to those in plasma are attainable. Fluconazole would be expected to achieve levels similar to those in plasma in both vaginal secretions and tissues to account for its success in the treatment of vaginal candidiasis. The aim of the present study was to determine the simultaneous levels of fluconazole in plasma and vaginal secretions in patients receiving treatment for vaginal candidiasis and to measure the rate of eradication of fungal infection. We also report the first use of a capillary gas chromatographic assay combined with ion trap detection for measurement of fluconazole in samples of small volume.From a group of patients participating in a multicenter study to determine the efficacy, safety, and toleration of fluconazole in the treatment of vaginal candidiasis (results of which will be published separately), patients who worked locally were approached for additional informed consent to enter this investigation. Only patients aged 18 years or older, with a clinical diagnosis of vaginal candidiasis (including symptoms of either vaginal pruritus or burning), who were willing to refrain from sexual intercourse until 7 days after fluconazole treatment were allowed to enter. Excluded were those who were either pregnant or lactating; had any other clinically relevant disease or impairment of renal or hepatic function; had concomitant venereal disease, trichomoniasis, or nonspecific vaginitis; were undergoing any other antifungal treatment; were taking any drugs that are cleared predominantly by metabolism and that have a low therapeutic ratio; or had taken any investigational drug in the previous month. Thus the first nine females (mean age, 30 years; range, 23 to 41 years) who agreed to return were enrolled in the study.Just before a patient received an oral 150-mg dose (three 50-mg capsules) of fluconazole, samples of blood and of vaginal secretion were taken. Further samples were taken at * Corresponding author. 2, 8, 24, 72, 120, and 168 h postdosing. Blood samples were collected in heparin tubes, and plasma was separated immediately by centrifugation and stored at -20°C until assayed. Vaginal secretion samples were collected by suction into...

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Turbulent flow chromatography coupled to tandem mass spectrometry (TFC-MS-MS) has recently emerged as a potentially fast, sensitive and specific technique for the direct analysis of pharmaceutical compounds from crude plasma. TFC-MS-MS removes the need for time-consuming sample preparation procedures such as solid-phase extraction (SPE) or liquid-liquid extraction (LLE). A relatively high flow rate combined with the use of an HPLC column with large porous particles allows the on-line clean up and quantification of compounds in plasma samples. Until now, the amount of plasma directly injected into TFC systems has rarely exceeded 30 IxL in order to prevent rapid column degradation. Increasing the injection volume also induces high carry-over levels, particularly fordrugs with basic and/or hpophilic properties. This paper describes the first generic TFC-MS-MS method developed in a 96-well format, which allows the direct injection of 200 I~L of 1:1 diluted plasma (equivalent to 100 I~L neat plasma). An average of 390 injections was carried out with each extraction column. More than 2000 clog plasma samples were injected into the system without any sign of carryover. The method was fully validated over a 5 -5 0 0 ng mL 1 range for three basic compounds: cloxazosin, CP122,288 and clofetilide. The imprecision was 1.2 to 8.3% for doxazosin, 1.5 to 4% for CP122,288 and 1.6 to 9.2% for dofetilide. The inaccuracy ranged from 6% to 7.9%. This generic methodology was then used to assay l",,vo structurally unrelated development compounds, showing that the method accuracy and sensitivif,/were adequate for the early pharmacokinetic (PK) studies in animals.