SIMULTANEOUS DETERMINATION OF HYDRAZINE, METHYLHYDRAZINE, AND 1,1-DIMETHYLHYDRAZINE IN RAT PLASMA BY LC–MS/MS

□ A rapid and sensitive analytical method of liquid chromatography combined with tandem mass spectrometry (LC–MS/MS) was established for simultaneous quantitative analysis of hydrazine, methylhydrazine, and 1,1-dimethylhydrazine in rat plasma. Plasma samples were pretreated with protein precipitation and optimized derivatization procedure. Separation was achieved using acetonitrile and water containing 5 mM ammonium acetate as gradient elution. The optimized mass transition ion-pairs (m/z) monitored for three hydrazine derivatives were m/z 299.1→m/z 151.1, m/z 180.2→m/z 78.1, and m/z 194.2→m/z 59.1, respectively. The lower limit of quantitation (LLOQ) of hydrazine was 1 ng/mL and those of other compounds were 10 ng/mL. Intra- and inter-day precision were within 14.00%. Meanwhile, the relative error was within the acceptable range. The recovery of three analytes and (IS) were between 57.78 ± 4.73%and 107.04 ± 7.46%. Target derivatives were stable under the conditions tested. The dilution test showed that this method is not only suitable for samples in the detection limit but also applicable for high concentration samples that exceed the upper limit of detection. The performance of the method was successfully verified for real rat plasmas and would be useful for routine analysis in cases of suspected hydrazine poisoning.