This paper reports a new qualitative analytical approach, based on a color reaction for the detection of nitrous oxide (N₂O), in order to solve problems of existing methods. The coloration was caused by the azo coupling of N₂O with a Grignard reagent and 1-naphthol in the presence of CuCl₂, which generated an orange-colored product 4-(phenylazo)-1-naphthol (4-PN) known as an azo dye compound. This color reaction provided both a simple color identification test and derivatization of N₂O for its effective identification by gas chromatography/mass spectrometry (GC/MS) or liquid chromatography/tandem mass spectrometry (LC/MS/MS). This approach has several advantages such as: N₂O was detectable by the color identification test quickly even when it was diluted with air, the derivative 4-PN was detectable by GC/MS or LC/MS/MS using an ordinary separation column and detection limits were about 10% for the color identification test, 1% for GC/MS, and 0.01% for LC/MS/MS. Thus, this method was found to be useful for both preliminary test and confirmation of N₂O in street drug samples.

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