A planar differential mobility spectrometer (DMS) was coupled to a Mini 10 handheld rectilinear ion trap (RIT) mass spectrometer (MS) (total weight 10 kg), and the performance of the instrument was evaluated using illicit drug analysis. Coupling of DMS (which requires a continuous flow of drift gas) with a miniature MS (which operates best using sample introduction via a discontinuous atmospheric pressure interface, DAPI), was achieved with auxiliary pumping using a 5 L/min miniature diaphragm sample pump placed between the two devices. On-line ion mobility filtering showed to be advantageous in reducing the background chemical noise in the analysis of the psychotropic drug diazepam in urine using nanoelectrospray ionization. The combination of a miniature mass spectrometer with simple and rapid gas-phase ion separation by DMS allowed the characteristic fragmentation pattern of diazepam to be distinguished in a simple urine extract at lower limits of detection (50 ng/mL) than that achieved without DMS (200 ng/mL). The additional separation power of DMS facilitated the identification of two drugs of similar molecular weight, morphine (average MW = 285.34) and diazepam (average MW = 284.70), using a miniature mass spectrometer capable of unit resolution. The similarity in the proton affinities of these two compounds resulted in some cross-interference in the MS data due to facile ionization of the neutral form of the compound even when the ionic form had been separated by DMS.