The manuscript by Wang and co-workers described the elucidation of forced degradation impurities in two antibiotics, cloxacillin and flucloxacillin, using tandem mass spectrometry. The authors report many impurities for both molecules, including both monomeric and dimeric structures.

Whilst the manuscript has scientific validity in revealing new understanding to better handle cloxacillin and flucloxacillin e.g. optimal storage conditions, at present it is far too long. Specifically, the bulk of the Results and Discussion is simply documenting the different precursor and product ions seen for each impurity. The format for each impurity is the same, making it repetitive for the reader. It’s not clear what value this adds to the information documented in tables 1-4? Furthermore, there is also no discussion about the relationships between different impurities, despite many structures being similar e.g. same neutral losses observed, certain moieties being lost when part of one structure but not in another and the reasons why. As it stands, the manuscript is documenting, rather than discussing and interpreting, the results much of the time.

As we as revising the reporting of the results, the authors may wish to consider the following points:

Page 3, line 29 This is not a conclusion. The sentence describes another aspect of study that was investigated. Please amend.

Page 3, line 39 “are” rather than “were” – these antibiotics are still in use.

Page 3, line 45 The first sentence of this paragraph is essentially a repeat of the last sentence of the previous one. Please amend.

Page 4, line 68 Why is obtaining accurate molecular weights important? The authors don’t explain that accurate mass measurement is needed to deduce elemental composition, which is the first stage of elucidating the structure of an unknown molecule.

Page 5, line 102 In which directions does the 2:1 split go? Two parts to waste, one to the mass spectrometer?

Page 6, line 106 By convention, m/z is shown before the value, not after it.

Page 6, line 123 “Respectively” used incorrectly in this sentence, and throughout the rest of this section. Both samples are treated the same. Respectively need only be used if different things apply to the two samples.

Page 6, line 144 “is” rather than “was” as phosphate is always inappropriate for MS analysis.

Page 6, line 154 “…were the most.” Most what? Numerous? Most abundant?

Page 8, line 185 “are” rather than “were”. Tense problems throughout the manuscript. Past tense should be used to describe the work done, present tense for the discussion of it.

Page 9, line 195 Typo – “the” rather than “The”.

Page 9, line 196 Can these structural features be shown in a figure please? This would make it much easier to understand.

Page 9, line 203 The term “molecular ion” means ions generated by the removal or addition of an electron, as defined by IUPAC (please see Murray et al., 2013, Pure Appl. Chem., 85, 1515-1609). “Precursor ions” would be a more appropriate description.

Page 9, line 206 “…was used to predict the…”. No prediction is made. The elemental formula is “deduced” or “determined” using the accurate mass measurement.

Page 9, line 215 Is there a specific reason that these two impurities were included in figures? Are they simply examples? Or is there significant to their selection?

Page 10, line 219 Figures 5, 6 & 7 are referred to before Figure 4. Figures should be described in numerically ascending order. Please amend.

Page 30, Figures 1 & 2 Need to annotate the ions in the mass spectra so that the reader understands what they are

Page 36, Tables 1 & 2 Molecular weight has no units. And is it meaningful to quote ppm to 2 d.p.?

Page 37, Tables 3 & 4 The data is accurate mass data, not exact mass (that is a theoretical value). How is “major” defined?