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Background:  1,3,5-trinitroperhydro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) can cause serious toxicity problems in humans and animals, but direct analyses of RDX and HMX in biological samples are very limited. A rapid and efficient liquid chromatography-electrospray quadrupole linear ion trap mass spectrometry (LC-MS/MS) method suitable for the simultaneous determination of RDX and HMX in rat plasma after intravenous administration of two nitramine compound mixed solutions has been developed.   Methods:  Plasma samples were pretreated with one-step protein precipitation, the plasma consumption is as low as 100 μl. RDX, HMX, and internal standard mycophenolic acid were eluted for 8.0 min on a reversed-phase C 18  analytical column with a water/acetonitrile mixture as the mobile phase. An electrospray ionization (ESI) source was applied and operated in negative ion mode. The optimized mass transition ion pairs (m/z) monitored for RDX, HMX, and internal standard mycophenolic acid were  m/z  284.1→61.7,  m/z  331.0→108.8,  and m/z  319.2→191.1, respectively.   Results:  The detection ranges of both RDX and HMX in plasma were 5.00–200.00 ng⋅ml −1  with an LOD of 1.00 ng⋅ml −1 . The extraction recoveries of RDX and HMX were 60.04 ± 4.18% and 79.57 ± 3.35%, respectively. The precision and accuracy met the requirements, and the method was stable under all tested conditions.   Conclusion:  The present method is miniaturized, effective, portable, rapid and can be easily used for simultaneous quantification of RDX and HMX in rat plasma.

Simultaneous Determination of RDX and HMX in Rat Plasma by LC-MS/MS and its Applications