Drug products and medical device extracts are chromatographically analysed via non-targeted analysis to detect, identify, and quantify organic leachables; GC/MS addresses primarily volatile and semi-volatile organic leachables. Identities of compounds detected by GC/MS are often secured by mass spectral matching (MSM), where the mass spectrum is compared to reference spectra from a spectral library. Compounds whose reference spectrum closely matches the analytical spectrum are candidate identities for the compound of interest. Even when rigorously applied, MSM can lead to incorrect candidate identities. Avoiding misidentifications is important as reporting misidentified compounds can severely impact toxicological risk assessment, potentially leading to false conclusions about patient safety.
The retention index (RI) is an effective means of evaluating an identity secured by MSM. The agreement between an experimental RI and a reference RI likely corroborates or refutes an MSM identity, although in certain cases the RI comparison may be inconclusive. The use of RI matching to corroborate MSM-based identities was investigated. Experimental and calculated RI values from the NIST23 library were compared to experimental RI values. Both classes of NIST23 RI values correlated well with the experimental RI obtained for 3140 compounds with confirmed identities, leading to the development of a strategy where reference RI-information from NIST23 can be used to support, accept, or reject candidate MSM structures.
Using a confusion matrix, it is concluded that within the boundaries set for mass spectral matching (MSM>85; top 5 ranked candidates), an absolute difference in RI between the experimental value and the NIST reference value (|ΔRI|) of equal or lower than 20 showed a high identification precision and corroborates proposed identified. A |ΔRI| value higher than 50 showed a very low precision, which consequently rejects these identifications. |ΔRI| values 3 between 20 and 50 are indiscriminate, meaning that while the identity proposed via MSM is accepted, it is considered to be tentative and uncorroborated.
