We propose a new approach to chemical gas analysis in the gas phase by direct referencing of a quantum cascade laser (QCL) to a near-infrared optical frequency comb. The concept was demonstrated through measurements of CO2 molecular densities, reaching a precision of 0.2 %. Thanks to the robust phase lock of the QCL to the comb, absorption profiles could be recorded with high accuracy and repeatability by tuning the repetition rate of the comb. Such a scheme gave us the opportunity to test a variety of semiclassical line-shape models, accounting for both Dicke narrowing and speed-dependent effects. The success of the speed-dependent Nelkin–Ghatak model, with a hypergeometric dependence of the pressure broadening coefficient on the absorber speed, was demonstrated. Finally, the dependence of molecular density determinations on the choice of the line-shape model was investigated, thus demonstrating the inadequacy of the Voigt profile.