The hyphenated technique liquid chromatography-mass spectrometry (LC-MS) is considered to be the method of choice for very broad application. However, the interference of chemical background (noise) observed in atmospheric pressure ionization (i.e. electrospray and chemical ionization) has been rencountered to be a problem for LC-MS trace (bio-)analysis. In our preliminary study, a novel technique has been developed to reduce the positive chemical noise in LC-MS, which is based on exclusive gas-phase reactions of background ions with a reactive collision gas (Guo et al. World Patent WO 2007/092873; Anal. Chem. 2007, 79, 4013-4021). The exclusive reactions lead to selective reduction of chemical noise in tandem triple quadrupole LC-MS. Investigations will focus on further characterization background noise, screening for suitable neutral reagetns, improvement of the chemical noise reduction technique, its implementation and application in trace bio-analysis.