Chronic low dose Adderall XR down-regulates cfos expression in infantile and prepubertal rat striatum and cortex.

We previously reported that treatment of prepubertal male rats with low, injected or oral, doses of methylphenidate stimulated cfos, fosB and arc expression in many areas of the developing brain. In the present study our objective was to determine whether the widely prescribed psychostimulant Adderall XR (ADD) exerted similar effects in infantile and prepubertal rat brain. We report here, for the first time, that low threshold doses of oral ADD, an extended-release mixture of amphetamine salts, now routinely used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), also increased cfos expression in infantile (postnatal day 10; PD10) and prepubertal (PD24) rat brain. These threshold doses were correlated with blood levels of amphetamine determined by liquid chromatography-mass spectrometry. Moreover, we observed that chronic treatment with oral ADD (1.6 mg/kg; x 14 days) not only significantly down-regulated cfos expression following a final challenge dose of ADD in prepubertal (PD24) rat striatum and cortex, quantified in terms of FOS immunoreactivity (FOS-ir), but did so at a daily dose that was without effect with methylphenidate (MPH); that is a much higher oral dose of MPH (7.5 mg/kg; x 14 days) failed to induce down-regulation of cfos expression. Similar experiments in infantile rats (PD10), but using a threshold injected dose of ADD (1.25 mg/kg sc) also significantly reduced striatal and cingulate cortical FOS-ir. An additional finding in the prepubertal rats was that oral ADD-induced FOS-ir was observed in the cerebral cortex following doses lower than the threshold dose necessary to increase FOS-ir in the striatum. This was not the case in the PD10 rats. In conclusion, our efforts to calibrate biological responses, such as immediate early gene expression, to clinically relevant blood levels of stimulants confirmed that expression of cfos is very sensitive to repeated low doses of Adderall XR. It is now feasible to examine whether other genes are also affected in these young rats and if the changes we report are reversible. The implications of such studies should be relevant to the putative effects of psychostimulant treatment of very young children.

Rapid SPME/LC/MS/MS analysis of N-methylcarbamate pesticides in water.

Solid-phase microextraction combined with fast short-column liquid chromatography/electrospray ionization tandem mass spectrometry (SPME/LC/MS/MS) was used for isolating and analyzing nine N-methylcarbamate pesticides from water samples. Several SPME parameters, such as polarity of fibers, extraction time, and effect of ionic strength, were investigated and their impact on the SPME/LC/MS/MS technique was studied. The method was shown to be sensitive with detection limits between 0.3 and 1.9 microg/L and reproducible with precision between 4.5 and 12.7% RSD. The versatility of the method was exhibited by its excellent linearity in the concentration range of 2-2,000 microg/L in drinking water. A comparison of the SPME/LC/MS/MS method with LC/MS/MS methods utilizing traditional sample preparation techniques shows that the former offers similar performance in terms of precision and linearity, but is clearly easier to use and faster to perform.

Study of erythromycin A decomposition products in aqueous solution by solid-phase microextraction/liquid chromatography/tandem mass spectrometry.

The decomposition of erythromycin A (EA) in aqueous solution was examined in the pH range 2-13 by means of combined solid-phase microextraction (SPME) and liquid chromatography/electrospray ionization tandem mass spectrometry. Degradation of EA, especially at lower pH values (pH < or = 3), was very rapid and yielded a wide variety of decomposition products. Identification of these degradation products was achieved by means of tandem mass spectrometry in the product ion and precursor ion scan modes. Anhydroerythromycin A was shown to be the major reaction product in both acidic and basic solutions. Among the different SPME fibers investigated for extraction from aqueous solutions, polydimethylsiloxane/divinylbenzene exhibited the best performance for EA and its degradation products.

Rapid determination of corticosteroids in urine by combined solid phase microextraction/liquid chromatography/mass spectrometry.

Solid-phase microextraction combined with fast short-column liquid chromatography/mass spectrometry (SPME/LC/MS) was used for isolating and analysing 11 corticosteroids and 2 steroid conjugates from urine samples. Several SPME parameters such as polarity of fibres, extraction time and effect of ionic strength, were investigated, and their impact on the SPME/LC/MS technique was studied. To demonstrate the potential of the SPME/LC/MS method, its application to the determination of steroids in human urine was investigated. The method was shown to be sensitive with detection limits between 4 and 30 ng/mL and precision between 4.9 and 11.1% RSD through the use of an internal standard technique. The versatility of the method was also exhibited by its excellent linearity in the concentration range of 20 to 20,000 ng/mL in urine for all investigated compounds. A comparison of the SPME/LC/MS method with LC/MS methods utilizing traditional sample preparation techniques, shows that the former offers similar performance in terms of precision, linearity and detection limits, but is clearly easier to use and faster to perform.