High-performance liquid chromatography with ultra violet and photo-assisted electrochemical detection (HPLC-UV-PAED) has been applied to the sensitive and selective determination of organic nitro compounds. The system was first developed for the determination of nitro explosives, and PAED has shown superior sensitivity over UV detection for these compounds (i.e., <1 part-per-trillion for HMX). The system also shows enhanced selectivity over the traditional UV method in that two detectors can be used for improved analyte identification. Also, having two detectors permits chemometric resolution of overlapping peaks, and this is not addressed in the UV method. Because this method is applicable to a wide range of nitro explosives, it was predicted that PAED would show the same sensitivity and selectivity toward other types of nitro compounds. Since its development, the system's use has been expanded to include the determination of nitro-containing pharmaceuticals and glycosylated nitro compounds in biological matrices. Model compounds were chosen, specifically nitroglycerin and related compounds and nitrophenyl-glucoside, to represent these classes. PAED showed superior detection limits over low wavelength UV detection for nitroglycerin (PAED = 0.3ppb, UV at 220nm = 48ppb), demonstrating PAED's applicability to determining nitro-pharmaceuticals. Conversely, UV detection at 220nm proved to be more sensitive than PAED for nitrophenyl-glucoside (UV at 220 = 0.6ppb, PAED = 3.6ppb). However, when nitrophenyl-glucoside was spiked into urine, PAED determination resulted in 99+0.3% recovery, while UV at 220nm resulted in 116+0.2% recovery, suggesting that UV determination may suffer from matrix interference.