Main comment
The manuscript describes an LC-HRMS method for screening multiple compounds in equine urine. Major revision is recommended before the manuscript can be considered for publication.

Specific comments
1. Similar methods have already been reported in the literature. The novelty of the work is not clearly presented in the manuscript. Please compare the present method with the reported methods to indicate the novelty of the current method. One example is the comparison between the two different SPE sorbents, leading to the selection of C18 sorbent.
2. Product ion scan (PIS) was mentioned several times in the manuscript. However, it is not clear if it was used for the screening. If it was, how was it used? Additionally, there are far less compounds with PIS in Table 2 than the compounds in Table 1. Please provide an explanation.
3. In the first paragraph of the introduction section, “IFHA” and “FEI”. The full name should be given for an abbreviation when it is first used.
4. In the first paragraph of the introduction section, “…cover a broad and wide range of controlled equine…”. The verb in this sentence should be in singular form.
5. In the fourth paragraph of the introduction section, a similar method by You Y and Proctor RM et al should be cited (Use of high resolution/accurate mass full scan/data-dependent acquisition for targeted/non-targeted screening in equine doping control, 2021 Analytical Methods, 13(13), pp. 1565-1575).
6. In section 2.2, “water or dimethyl sulfoxide (DMSO), water to”. Water is mentioned twice in this sentence. Please double check.
7. In the third paragraph of section 3.1, “after evaluating various columns with different stationary phases”. What columns were evaluated? Why were other columns not chosen? Please provide more details.
8. In the fourth paragraph of section 3.1, “All of the ion source parameters were optimized by approximately 25 representative analytes”. How were the source parameters optimized with the 25 representative analytes? Please provide more details.
9. In the fifth paragraph of section 3.1, “TraceFinder (Version 5.1), was used for data processing”. This software was used for data processing in a publication by You Y and Proctor R et al. It should be mentioned.
10. In the second paragraph of section 3.2, “with MEs ranging from 0.5 to 954% whereas ionization suppressions were also recorded with MEs between −0.3 and −93.7%.” According to the ME calculation statement in section 2.6, no negative value should be generated. Please check the values.
11. In Table 1 legend, “[M]+”, “[M-HCOOH+H]+”, and [M-COOH]-“. It seems that these ion notations are incorrect. Please double check.
12. The fonts in Table 1 are too small to be seen. Please make the fonts larger to be visible. Table 1 may be too long to be included on the journal pages. Please consider placing Table 1 in supplementary information.