Hydrazine and Hydrazine derivatives are used in many applications, including as therapeutic agents. Isoniazid, for example, is a Hydrazine derivative used as an anti-tubercular drug that can potentially metabolize to Hydrazine or Acetylhydrazine. As such, there is demand for a quantitative analysis method of these compounds in a pharmaceutical setting where HPLC/MS/MS is often employed. HPLC/MS has not been widely studied for the detection of Hydrazine, in part due to the molecule’s polarity and low molecular weight. In this work, we report the quantitative analysis of Hydrazine and Acetylhydrazine by HPLC/MS/MS using chemical derivatization with 4-Bromobenzaldehyde to produce the corresponding Azine and Hydrazone products. The products are easily extracted and reconstituted in an Acetonitrile:H2O solvent suitable for HPLC/MS/MS detection.