Analytical Methods for Monitoring Traumatic Brain Injury Biomarkers/treatment and Pharmaceutical Residual Solvents

"The development of highly sensitive and efficient analytical methods utilizing advanced instrumentation is necessary to help improve disease diagnosis and therapeutics. A major neuro-consequence of traumatic brain injury (TBI) is oxidative stress from the generation of reactive oxygen species and the depletion of antioxidant defenses. Alteration in concentrations of certain small molecules also occurs with the disease progression and can help understand TBI pathophysiology. Two analytical methods employing liquid chromatography with tandem mass spectrometry (LC-MS/MS) were developed and validated to monitor the potential small-molecule TBI biomarkers at sub-ppb levels. Subsequently, the neuroprotective effect of an antioxidant prodrug, N-acetylcysteine amide (NACA), was evaluated in rat models that were exposed to the blast-induced TBI from open-field blasts simulating what military personnel are regularly exposed to in combat. The benefit of antioxidant pretreatment was indicated by the significantly lower levels of biomarkers detected in rat urine, plasma, and brain tissue.Pharmaceutical manufacturers utilize solvents at different stages of production. Some of these harmful solvent residues can be retained in the final products and need to be monitored to meet regulatory requirements. A novel method for the rapid analysis of residual solvents in pharmaceutical products was developed by employing a compact and portable gas chromatography with a photoionization detector (GC-PID). The method detection limits for selected residual solvents in over-the-counter drugs were significantly lower than the compliance concentration limits. The validation of the new method yielded excellent accuracy, precision, and linear response" -- Abstract, p. iv