An LC/MS method for the quantitative determination of 7alpha-OH DHEA and 7beta-OH DHEA: an application for the study of the metabolism of DHEA in rat brain.

Dehydroepiandrosterone (DHEA) is an important neurosteroid with neuronal protection and memory enhancement functions. 7alpha-OH DHEA and 7beta-OH DHEA are the two important metabolites of DHEA in the brain. We have developed an LC/MS method to quantitatively analyze 7alpha-OH DHEA and 7beta-OH DHEA. Chromatographic separation was carried out on a C18 column with gradient elution using mobile phases of formic acid in acetonitrile and in water formic acid. Mass spectral detection was performed with a ThermoFinnigan LCQ advantage quadruple ion trap mass spectrometer with electrospray ionization. Positive ion chromatograms were acquired using single ion monitoring. The protonated molecule was 305 m/z, but the most abundant ion (269 m/z) was used for quantification. This method was validated and applied to investigate the 7-hydroxylation of DHEA. When incubating DHEA with rat brain microsomes, both 7alpha-OH DHEA and 7beta-OH DHEA were observed, but 7alpha-OH DHEA was the major metabolite.

Identification of a metabolite of atrazine, N-ethyl-6-methoxy-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, upon incubation with rat liver microsomes.

Atrazine is an herbicide which has shown potential antimalarial effects both in vitro and in vivo in rats. In order to study the metabolism of atrazine in rat livers, we developed a sensitive LC/MS/MS method for the identification of atrazine and several of its metabolites. Using this method, we identified one previously unreported metabolite with a mass of 211 Da in addition to two known metabolites. This new metabolite was confirmed to be N-ethyl-6-methoxy-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, also known as atraton, by comparison of the LC/MS/MS mass spectra and the retention time to those of a commercial standard.

A randomized crossover study investigating the influence of ranitidine or omeprazole on the pharmacokinetics of cephalexin monohydrate.

Limited data characterize pharmacokinetic interactions between cephalexin and ranitidine, and no data exist for an interaction with proton pump inhibitors. The purpose of this study was to investigate the effects of ranitidine or omeprazole administration on the pharmacokinetics and pharmacodynamics of cephalexin. A randomized single- and multiple-dose crossover study was conducted in healthy subjects ingesting cephalexin before and after steady-state administration of ranitidine or omeprazole. Time-concentration profiles were determined and pharmacokinetic parameters were characterized using noncompartmental methods. Pharmacokinetic data were analyzed in accordance with the two 1-sided test for bioequivalence. The percentage of time that serum concentrations remain above the MIC(90) during the dosing interval (T > MIC(90)) for Streptococcus pyogenes and Staphylococcus aureus associated with the pharmacokinetic profiles was calculated. The coadministration of cephalexin with ranitidine or omeprazole resulted in relatively minor changes in C(max), AUC(infinity), t(1/2), or CL/F. t(max) was significantly prolonged when cephalexin was administered with ranitidine or omeprazole. Suboptimal T > MIC(90) was observed for cephalexin irrespective of acid suppression. Delay in absorption of cephalexin resulted in a decrease in the percentage of T > MIC(90) for certain acid-suppressive regimens and pathogen combinations. With the exception of an increase in t(max), there were no significant pharmacokinetic interactions between cephalexin and ranitidine or omeprazole. Delayed t(max) associated with acid suppression may result in a diminished T > MIC(90).

Stability of phenytoin sodium suspensions for the treatment of open wounds.

The objective of this study was to evaluate the stability of two phenytoin sodium suspensions in 0.9% sodium chloride solution for use in noninstitutional settings (where pharmacies are not present) to dispense phenytoin on a daily basis. A generic extended phenytoin sodium (Mylan) and a name brand phenytoin sodium (Dilantin) in suspension form were evaluated. Both suspensions were first assessed for degradation during frozen storage at designated time intervals. Frozen samples were compared with freshly prepared samples. The chemical stability of phenytoin concentration in the samples was assessed by using a high-performance liquid chromatography analytical technique. During the course of the experiment, the samples showed no crystallization and the pH remained in a range of 10.6 to 10.73. The suspensions were tested for contamination. The results show that Dilantin and Mylan suspensions remained stable and free of contamination. Suspensions of phenytoin sodium in 0.9% sodium chloride solution are stable at room temperature for at least 2 weeks.