An ecofriendly and sensitive SFC MS/MS method (using TurbolonSpray probes) has been developed to measure Isonaizid (INH) and pyrazinamide (PYZ) in fix dosage combination (FDC) by dissolving in dichloromethane:methanol:formic acid (50:50:0.1 v/v/v). Supercritical carbon dioxide (SC-CO2) is used as mobile phase at a flow rate of 2 ml/min and modifier used is dichloromethane:methanol:formic acid (50:50:0.1 v/v/v) at a flow rate of 0.3 ml/min. High penetration power, low viscosity, negligible toxicity makes the obvious choice for environment friendly mobile phase. The separation of INH and PYZ was achieved in less than 5 min using a C18 reverse-phase fused-core column (Inertsil ODS-5 pan C18, 150 mm x 4.6 mm). The method was validated as per international standards in terms of selectivity, linearity, precision and recovery. The method was found to be linear and % recovery was found to be 98.89-100.33% and 99.27-100.06% for INH and PYZ, respectively. Lower limits of detection and quantification could be achieved for INH was 11.87 ng/ml and 35.97 ng/ml, respectively, and for PYZ was 35.42 ng/ml and 107.36 ng/ml, respectively. The proposed method was applied to the marketed formulation of different manufacturers. (C) 2014 Elsevier B.V. All rights reserved.