Fabrication and Applications of Potentiometric Membrane Sensors Based on γ-Cyclodextrin and Calixarene as Ionophores for the Determination of a Histamine H1-Receptor Antagonist: Fexofenadine
Round 1
Reviewer 1 Report
Authors have modified the manuscript, and definitely it was improved after the revision, but some minor issues are stil remaining. The tables 2-4 are not uniform, in table 2 and table 4 authors report data corresponding to sensor 1 and sensor 2 as columns, in table 2 (ex-Table 1 for which a suggestion to replace columns with lines was done), the data are remained in lines. This mixed representation os confusing. SSM is separate solution method, and not "separate separation"! - see Table 3 (*-marked clarification below the table 3, it was already noted to authors but they did non change this typos). Moreover, authors must add the standard deviation value for all the slopes reported in tables 1,2,4, and indicate a number of repetitions . The standard deviation are provided for Intersept in Table 4, but not for slope! The caption f a new Figure 2 is not legible. After this corrections paper can be published in Membranes.
Author Response
Reviewer 1
1.The tables 2-4 are not uniform
Answer
The tables 2-4 have been uniformed and the data are inserted in columns.
- SSM is separate solution method, and not "separate separation"! - see Table 3 (*-marked clarification below the table 3, it was already noted to authors but they did nonchange this typos).
Answer
Marked clarification in Table 3 has been corrected (separate solution method).
3.Moreover, authors must add the standard deviation value for all the slopes reported in tables 1,2,4, and indicate a number of repetitions. The standard deviation is provided for Intercept in Table 4, but not for slope!
Answer
The standard deviation value for all the slopes reported in tables 1,2, and 4 has been inserted.
- The caption f a new Figure 2 is not legible.
Answer
The caption of Figure 2 has been modified to be legible.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Manuscript is improved and can be published in its present form.
Author Response
The response is OK
Reviewer 3 Report
The manuscript reported the design of a potentiometric sensor for the selective detection of fexofenadine. The various parameters of pH, time response, reproducibility, and accuracy of sensors 1 and 2 were studied. The manuscript is well-written and organized.
Please see the following comments:
1- It is highly recommended to address the work novelty.
2- The figure 2 caption is overlapped on the Figure 1A labeling. Please check and revise.
3- The pH range is too wide from 2 to 8. It is highly recommended to specify the best detection pH for sensors 1 and 2.
4- The mode of action for the selective response of fexofenadine molecules is unclear. It is highly recommended to address this point.
5- It is highly recommended to address sensors 1 and 2 differences and the mode of action.
The manuscript's English language is good
Author Response
Reviewer 3.
1- It is highly recommended to address the work novelty.
Answer
The novelty of the work has been addressed (P.2 lines 83-88).
2- The figure 2 caption is overlapped on the Figure 1A labeling. Please check and revise.
Answer
Figure 2 caption has been revised.
3- The pH range is too wide from 2 to 8. It is highly recommended to specify the best detection pH for sensors 1 and 2.
Answer
Although fexofenadine has two ionization groups corresponding to the free carboxylic group on the side chain (pKa = 4.25) and the substituted ring nitrogen (pKa = 9.53), Therefore, the suitable working pH was a wide range, and the optimum pH for both sensors is 2-4, which agrees with the most published methods [26–29] and has been corrected in the manuscript.
4- The mode of action for the selective response of fexofenadine molecules is unclear. It is highly recommended to address this point.
Answer
Selectivity response of fexofenadine has been inserted in the manuscript (P. 7 Lines 188-197).
5- It is highly recommended to address sensors 1 and 2 differences and the mode of action.
Answer
Both ionophores belong to the same class of cyclic compounds known as cavitands in host-guest chemistry (supramolecular chemistry). Therefore, both ionophores have the same mode of action, and the difference is related to different chemical structures (as stated in the introductions P1 and P2).
Author Response File: Author Response.pdf
Round 2
Reviewer 3 Report
The authors have been raised most of the comments. So, I recommend accepting the manuscript in the current form
The English language is acceptable
