Effective on October 2011, the new SAMHSA/NIDA guidelines allow implementation of LC-MS technique to perform NIDA-5 panel, urine quantitative confirmatory analysis. LC-MS/MS methods are often less complicated than the previously implemented GC-MS/MS methods because they do not require derivatization. The NIDA-5 panel requires 6 separate quantitative methods for analysis of THCA, opiates, amphetamines, cocaine, phencyclidine and 6-MAM to confirm immunomethod positive samples. Here we developed 6 methods using a single sample preparation procedure, analytical column, mobile phase and instrument configuration. The methods are implemented on new Thermo Scientific™ dual channel Prelude ™ SPLC online sample preparation-liquid chromatography system, which allows method execution in parallel with a different method on each channel or the same method on both channels multiplexed to a single mass spectrometer.