Eight commonly used sulfonylureas (SUs:  nicosulfuron, thifensulfuron methyl, metsulfuron methyl, sulfometuron methyl, chlorsulfuron, bensulfuron methyl, tribenuron methyl, and chlorimuron methyl) and deuterium-labeled nicosulfuron (nicosulfuron-d(6)), used as an internal standard, were isolated from soil by solvent extraction and identified under quantitative and qualitative ion spray LC/MS/MS conditions using the selected reaction monitoring (SRM) mode of acquisition. The lower level of quantitation for these SUs in soil was determined at the 0.05 ppb level using a TurboIonSpray adapted LC/MS interface without a precolumn split and optimizing MS/MS tuning conditions for individual SUs. The eight SUs were qualitatively identified and quantitatively determined in soil. The standard curve for each SU was linear from 0.05 to 10 ppb. This SRM LC/MS method demonstrates high sensitivity and high specificity for these SUs in soil and shows at least a 400-fold improvement in sensitivity over previous reports. Acceptance criteria for forensically valid data are suggested for qualitative SRM LC/MS experiments. These include HPLC retention time reproducibility (±2%), at least two and preferably three precursor-product ions selected, and relative abundance criteria for selected ions (±20% absolute).

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The absolute bioavailability (F) and dose proportionality of cefprozil were investigated in a parallel design study with an embedded two-way crossover leg. Twenty-four healthy male subjects divided into 3 dosing groups received a single 250-, 500-, or 1000-mg dose of cefprozil by a 30-minute intravenous infusion. Subjects assigned to the 500-mg dose group also received a 500-mg oral dose of cefprozil in crossover manner with a wash-out period of 7 days between each treatment. Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. Serial blood and urine samples were collected and analyzed for the concentrations of the cis and trans isomers of the cephalosporin using high-pressure liquid chromatographic assay with UV detection methods. After the 250-, 500-, and 1000-mg intravenous administration of cefprozil, the peak concentrations were 13.2, 26.0, and 48.5 micrograms/mL, and area under the plasma concentration versus time profiles were 17.2, 31.4, and 58.1 micrograms.hour/mL, respectively, for the cis isomer increasing in a dose proportional manner. Total body clearance, renal clearance, and volume of distribution at steady state, adjusted for body weight, were not significantly different among all groups. Mean residence time, elimination half-life, and urinary recovery were invariant with the dose. Based on the plasma and urine data, the estimates of F were 89% and 94% for the cis isomer, respectively. The plasma concentrations of the trans isomer were about 1/10th of the cis isomer, and all parameters were similar to those observed for the cis isomer. In summary, cefprozil exhibits linear pharmacokinetics and is essentially completely absorbed after oral administration.

The excretion of cefprozil into breast milk in nine healthy, lactating female subjects was investigated. Each subject received a single 1,000-mg oral dose of cefprozil consisting ofcis and tramns isomers in an approximately 90:10 ratio. Serial blod, urine, and breast milk samples were collected and analyzed for the concentrations of the cis and trns isomers by a specific high-pressure liquid chromatography-UV assay. The mean pharmacokinetic parameters for both isomers were essentialy the same. The mean peak concentrations in plasma for the cis isomer were 14.8 Fg/ml, and the area under the concentration curve was 54.8 ,ug* h/mi. The mean values of elimination half-life, renal clearance, and urinary excretion for the cis isomer were 1.69 h, 164 mI/min, and 60%, respectively. The mean concentrations in milk of the cis isomer over a 24-h period ranged from 0.25 to 3.36 pg/ml, with the maximum concentration appearing at 6 h after dosing. The average mamum concentration in milk of the twas isomer was less than 0.26 pg/ml. The concentrations of the twans isomer in plasma and in breast milk were about 1/10 of those for the cis isomer. Less than 0.3% of the dose was excreted in breast milk for both isomers of cefprozil. Even if one assumes that the concentration of cefprozil in milk remains constant at 3.36 pig/ml (the highest concentration of cefprozil observed in breast milk), an infant ingesting an average of 800 ml of milk per day will be exposed to a maximum amount of about 3 mg of cefprozfl per day. This value represents about 0.3% of the maternal dose. Low excretion of cefprozil in breast milk and the excellent safety profile of cefprozil suggest that this cephalosporin may be administered to nursing mothers when indicated.Cefprozil is an oral cephalosporin consisting of cis and trans isomers in an approximately 90:10 ratio. The structure is similar to that of other oral cephalosporins with a propenyl side chain. Cefprozil has a broad antimicrobial spectrum. It is reported to be more active than cefaclor and cephalexin against streptococci, Listeria monocytogenes, and Hae-

A high-performance liquid chromatographic assay was developed and validated for a simulataneous determination of 2'-fluoro-2' 3'-dideoxyadenosine (FddA) and its metabolite, 2'-fluoro-2',3'-dideoxyinosine (Fddl) in dog plasma and urine. In vitro, FddA and Fddl exhibit activity against human immunodeficiency virus (HIV). A solid phase extraction was applied to extract FddA, Fddl, and the internal standard (IS; 3',5'-anhydrothymidine) from the biomatrices. The processed samples were chromatographed using a C8 column coupled with a mobile phase consisting of monobasic phosphate, dibasic phosphate, ethylene glycol monomethyl ether, and water. Detection was performed at 257 nm. The nominal retention times were 9, 14, and 26 min for Fddl, IS, and FddA, respectively. The lower limits of quantitation were 0.1 and 2.0 micrograms/mL in plasma and urine, respectively, for both analytes. The accuracy of the assay deviated < or = 10% from the nominal concentrations, and the precision was < or = 14% coefficient of variation. In either matrix, both analytes were stable for at least three freeze-thaw cycles and in the injection media for at least 54 h. The extraction recoveries of the analytes were greater than 80%. The application of this assay was demonstrated in a preliminary pharmacokinetic study of FddA and Fddl in dogs. Two male dogs per dose level received a 100, 250, or 500 mg/kg oral dose of FddA once daily for 14 days. The early appearance of Fddl in plasma (0.25 h; the first sampling time) and greater plasma levels of Fddl than FddA (> 50-fold of Cmax), suggested that the conversion of FddA to Fddl was rapid and extensive. Renal excretion appeared to be the major route of elimination of Fddl.