Estimating the time since discharge of spent cartridges can be a valuable tool in the forensic investigation of firearm-related crimes. To reach this aim, it was previously proposed that the decrease of volatile organic compounds released during discharge is monitored over time using non-destructive headspace extraction techniques. While promising results were obtained for large-calibre cartridges (e.g., shotgun shells), handgun calibres yielded unsatisfying results. In addition to the natural complexity of the specimen itself, these can also be attributed to some selective choices in the methods development. Thus, the present series of paper aimed to more systematically evaluate the potential of headspace analysis to estimate the time since discharge of cartridges through the use of more comprehensive analytical and interpretative techniques. Specifically, in this first part, a method based on headspace sorptive extraction (HSSE) was comprehensively optimised and validated, as the latter recently proved to be a more efficient alternative than previous approaches. For this purpose, 29 volatile organic compounds were preliminary selected on the basis of previous works. A multivariate statistical approach based on design of experiments (DOE) was used to optimise variables potentially involved in interaction effects. Introduction of deuterated analogues in sampling vials was also investigated as strategy to account for analytical variations. Analysis was carried out by selected ion mode, gas chromatography coupled to mass spectrometry (GC–MS). Results showed good chromatographic resolution as well as detection limits and peak area repeatability. Application to 9 mm spent cartridges confirmed that the use of co-extracted internal standards allowed for improved reproducibility of the measured signals. The validated method will be applied in the second part of this work to estimate the time since discharge of 9 mm spent cartridges using multivariate models.