Original articles
SHI Yuanai, SHI Fujiang, SONG Feiling, LI Yajuan, LIAO Sha, DU Kehe, YIN Jiye
Objective To establish a rapid and sensitive liquid chromatography-tandem mass spectrometry（LC-MS/MS）analysis method for determination of unsymmetrical dimethylhydrazine（UDMH）contents in rat plasma and investigate the toxicokinetic characteristics of UDMH in rats. Methods Twenty-two SD rats were divided into the intravenous injection of 10 mg/kg dose group（4 females）and intragastric administration groups（low, medium and high dose, with 6 rats in each group, half males and half females）. The rats were given 10mg/kg by intravenous administration and 10 mg/kg, 30 mg/kg, and 90 mg/kg single dose of UDMH by gavage. Blood samples were collected from the orbital venous plexus at 0 hour before administration and at different time points after administration. The plasma samples were extracted with protein precipitation and derivatization before being analyzed using the LC-MS/MS method. Separation was carried out on a ZORBAX column（4.6mm×75mm, 3.5 µm）, with a mobile phase composed of 0.3% acetonitrile/formic acid at a flow rate of 1 mL/min. Propranolol was used as the internal standard. An electrospray ionization（Turbo Ionspray）source was applied and the mass spectrometer was operated in a positive MRM mode. Quantitative analysis showed that the ionization source unsymmetrical dimethylhydrazine and propranolol was at m/z：192.0→148.1, m/z：260.2→116.1, respectively. The toxicokinetic parameters were analyzed with the DAS 2.1 software. Results Quantification of UDMH exhibited a good linearity within the concentration range of 50-50000 ng/mL, with a linear correlation coefficient greater than 0.9900 and a lower limit of quantification of 50 ng/mL. The average recovery rate of UDMH was 98.1%, compared with 100.5% for the internal standard propranolol hydrochloride. The inter batch precision of standard curve samples ranged from 0.7% to 6.3%, and the relative error was between -7.1% and 6.2%. The inter batch and intra batch precision of quality control samples ranged from1.8% to 19.8%, and the relative error from -9.8% to 0.2%. The main pharmacokinetic parameters of UDMH in rats exposed to 10 mg/kg,30 mg/kg, and 90 mg/kg gavage were UC（0-t）：（7624.99±2569.31）,（34284.04±6657.15）,（84720.88±22354.80）µg/L·h,t1/2：（0.07±0.15）,（2.24±1.45）,（3.04±0.90）h,Tmax：（0.75±0.27）,（0.51±0.29）,（0.29±0.10）h,Cmax：（4454.14±1329.45）,（19442.45±9121.07）,（32334.35±9882.41）µg/L, F：（77.34±26.06）%,（115.92±22.51）%,（95.48±25.19）%. Conclusion The LC-MS/MS method is highly accurate and specific, and is suitable for the toxicokinetic study of UDMH in rats. Single gavage administration of UDMH results in absorption and elimination saturation at a high dose. This study provides data for toxicological studies related to UDMH.
