Chemical markers, such as furanone, are intrinsically formed in foods at elevated process temperatures, and have been successfully used as indirect indicators of heating patterns in advanced thermal proces-ses such as aseptic processing, microwave sterilization and ohmic heating. However, very limited information is available on suitability of these chemical markers during combined pressure–heat treatment. The present study was conducted on the formation and stability of chemical marker M-2 (4-hydroxy-5-methyl-3(2H) furanone, a by-product of Maillard reaction) as a function of pressure, temperature and pH. Whey protein gels (containing 1g ribose/100g gel mix) at pH 6.1 and 8.3 were subjected to pressure assisted thermal processing (PATP; 350 and 700 MPa, 105 °C), high pressure processing (HPP; 350 and 700 MPa, 30 °C) and thermal processing (TP; 0.1 MPa, 105 °C) for different holding times. Unprocessed gel was used as control. The marker yield was quantified using HPLC. The initial concentrations of M-2 in the gels were 9.17 and 6.1 mg/100 g at pH 6.1 and 8.3, respectively. As expected, heat treatment at 105 °C, 0.1 MPa increased M-2 concentration. The marker yield increased with increase in holding time, following a first order kinetics and decreased with increasing pH. Pressure treatments from 350 to 700 MPa at 30 °C reduced the chemical marker formation for both pH values investigated. Marker formation during combined pressure-temperature (105 °C, 350 and 700 MPa) was influenced by both heat (which favored the marker formation) and pressure (which hindered marker formation). The net final concentration of the marker formed during PATP was higher than HPP, but lower than thermal treatments. This study suggests that 4-hydroxy, 5-methyl, 3(2H) furanone may not be a suitable marker for evaluating pressure–heat uniformity during PATP.