摘要:

SummaryThe authors report testing the meconium of a newborn for the presence of FAEE. Meconium from a newborn of a woman who acknowledged drinking beer throughout pregnancy was tested. The authors also tested the meconiums of 3 newborns whose mothers did not drink at all while pregnant. The FAEE were extracted from the meconium samples using solid phase extraction (SPE), and were identified and quantitated by gas chromatography with flame ionization detection (FID). For assignment of retention times and determination of individual concentrations, authentic mixtures of FAEE were injected. The total FAEE concentration in the meconium of the alcohol-exposed infant was 13126 ng/g compared to a mean of 410 ng/g in the control meconiums. Also, in this case, palmitic, linoleic, and stearic ethyl esters were found in the alcohol-exposed infant's meconium while they were not found in the unexposed infant's meconium. In a parallel experiment, the authors spiked increasing amounts of ethyl alcohol (0–40mM) into the meconium from a newborn that was not exposed to ethanol in utero. The spiked samples were incubated for 4 hours at 37°C and subsequently assayed for the presence of ethyl linoleate. In these experiments, they document for the first time that FAEE is produced in meconium. If confirmed by large studies, FAEE may become the first neonatal biologic marker for babies at risk for alcohol-related birth defects.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryThe authors describe a simplified high-performance liquid chromatographic (HPLC) method for the determination of gentamicin sulfate (GEN) in microsamples of plasma using 9-fluorenylmethyl chloroformate (FMOC) as a derivatizing agent and neomycin sulfate as the internal standard (IS). The drug and IS were separated on a 4 &mgr;m (particle size), 8 × 100 mm Nova-Pak C18 radial compression cartridge using a mixture of 84.5% acetonitrile and 15.5% water at a flow rate of 2.5 mL/min. The compounds were detected fluorometrically in the effluent at excitation and emission wavelengths of 260 nm and 315 nm, respectively. Sample preparation was performed on 50 &mgr;L of plasma using a simple liquid–liquid extraction followed by a room-temperature derivatization procedure. No interference from any endogenous substance or concurrently used drug was observed, and the retention times of the IS and three major components of GEN were 12.4, 19.5, 23.6, and 27.6 min, respectively. The concentration of the GEN in plasma for the range of 0.2–20.0 &mgr;g/mL was linearly (r> .997) related to the peak height ratio of the sum of the three major GEN peaks to that of the IS, with CV value at 0.3, 7.5, and 15 &mgr;g/mL being <3.61%. A comparison of the results from this assay versus fluorescence polarization immunoassay (TDx) showed a close agreement between the two methods withr= 0.994. This assay is currently being used to monitor GEN and investigate its pharmacokinetics in pediatric patients.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryA description of a quantification performance by laboratories taking part in two intercollaborative studies (surveys 1 and 2) carried out in 1993 (n = 195) and 1994 (n = 228), respectively, on urine drug testing in the European Union is presented. The performance of laboratories that quantified at least one substance (33.8% and 34.6% out of the total laboratories in surveys 1 and 2, respectively) is reported as a function of the analytic technique applied for quantification, the number of parameters investigated, the precision and accuracy of results obtained, and the influence of availability of reference material, including deuterated drug–standard analogue solutions provided in survey 2. Quantification of different drugs of abuse was mainly carried out by gas chromatography coupled to mass spectrometry (63.1% of analyses in survey 1 vs. 68.6% in survey 2). It should be noted about the data obtained that the results for quantification were not particularly satisfactory in terms of precision and accuracy (CV mean = 62.8 in survey 1 and 50.4 in survey 2 and error % mean = 12.7 in survey 1 and 18.6 in survey 2). The provision of reference materials increased the number of substances quantified (45.3% in survey 1 vs. 51.8% in survey 2) and improved the performance (CV mean of matching laboratories when quantifying matching substances: 50.1% in survey 1 vs. 35.5% in survey 2). The impact of a “learning factor” (the opportunity to be challenged a second time and to correct past errors) and the influence of the provision of deuterated analogues in survey 2 was investigated in a population of repeater laboratories that quantified both in surveys 1 and 2 (55 vs. 63 laboratories, respectively). According to the European experience reported, it may be observed that laboratories able to afford quantitative analyses provided better overall analytic performance. This is probably because quantification implies some validation of the analytic procedure. Participation in interlaboratory comparison programs also aimed at assessing the performance of quantitative analyses should be considered a quality asset for laboratories involved in drug testing.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryBlack renal transplant recipients have inferior graft outcomes when compared to whites. The relative bioavailability of cyclosporine (CsA) with the Sandimmune (SIM) formulation is lower in black recipients when compared to whites. To study relative CsA bioavailability in the Neoral formulation, 18 black and 78 white de novo renal transplant recipients were randomized in a multicenter, double-blind, parallel group study to receive either SIM or Neoral capsules twice a day for 12 weeks. After an overnight fast, CsA whole blood levels (TDx) were collected during 12 hours after the morning dose and 12 hours after the evening dose with a standardized meal. Pharmacokinetic profiles were obtained at the end of weeks 1, 4, 8, and 12. Initial CsA dose was 5 mg/kg twice a day; subsequent doses were titrated to target trough CsA levels. Area under the blood concentration vs. time curve (AUC), peak blood concentration (Cmax) and time to Cmax(Tmax) were obtained from 16 black and 73 white patients. Food conditions (fed and fasting) were averaged, and data was dose-normalized. For black recipients, Neoral was significantly more bioavailable than SIM only during week 1; there was also a consistent trend to higher cyclosporine bioavailability at weeks 4, 8, and 12. For whites, there were significant differences in favor of Neoral at all time periods. No significant differences in relative bioavailability were noted between races for either SIM or Neoral except for a higher Cmaxin white patients given Neoral. Neoral is better absorbed than SIM in both blacks and whites. These data suggest that Neoral is the superior CsA preparation for all racial groups.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryAn isocratic, high-performance liquid chromatography method has been developed for simultaneous determination of the oral antidiabetic tolbutamide and two of its metabolites, 4-hydroxytolbutamide and carboxytolbutamide, in human plasma and urine. The method was based on simple one-step liquid–liquid extraction with tertiary-butyl methyl ether as extraction solvent. The chromatographic eluent was 23:77 (v/v) methanol: 0.01 M aqueous sodium acetate buffer pH 3.0, and the UV detection was performed at a wavelength of 230 nm. The limit of detection was 0.1 &mgr;M for tolbutamide in plasma and 1.5 &mgr;M, 0.5 &mgr;M, and 0.75 &mgr;M for carboxytolbutamide, 4-hydroxytolbutamide, and tolbutamide, respectively, in urine. The limit of quantitation was 0.5 &mgr;M for tolbutamide in plasma and 2 &mgr;M, 0.75 &mgr;M, and 1.25 &mgr;M for carboxytolbutamide, 4-hydroxytolbutamide, and tolbutamide, respectively, in urine. The overall mean recoveries ranged from 91% to 109% for tolbutamide in plasma and from 80% to 98% in urine for all three compounds.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID