Development of a novel and cost-effective redox sensor for voltammetric determination of pantoprazole sodium during pharmacokinetic studies

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Development of a novel and cost-effective redox sensor for voltammetric determination of pantoprazole sodium during pharmacokinetic studies Pakinaz Y. Khashaba, Hassan Refat H. Ali and Mohamed M. El-wekil Article citation details R. Soc. open sci. 4: 170324. http://dx.doi.org/10.1098/rsos.170324 Review timeline Original submission: 10 April 2017 Revised submission: 15 June 2017 Final acceptance: 3 July 2017 Note: Reports are unedited and appear as submitted by the referee. The review history appears in chronological order. Review History RSOS-170324.R0 (Original submission) Review form: Reviewer 1 Is the manuscript scientifically sound in its present form? Are the interpretations and conclusions justified by the results? Is the language acceptable? Is it clear how to access all supporting data? Do you have any ethical concerns with this paper? No 2017 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited

2 Have you any concerns about statistical analyses in this paper? I do not feel qualified to assess the statistics Recommendation? Major revision is needed (please make suggestions in comments) Comments to the Author(s) The Comments are presented in attached file. (Appendix A) Review form: Reviewer 2 Is the manuscript scientifically sound in its present form? Are the interpretations and conclusions justified by the results? Is the language acceptable? Is it clear how to access all supporting data? Do you have any ethical concerns with this paper? No Have you any concerns about statistical analyses in this paper? No Recommendation? Accept with minor revision (please list in comments) Comments to the Author(s) It is a very interesting study on how bromocresol green modifications of pencil electrodes improve the determination of pantoprazol. Many parameters have been studied. The sensor was applied in challenging real samples like blood plasma, and even a pharmacokinetic study in rabbit was conducted. Analytical performance is quite impressive. The LOD of 22 nm is supported by the data. I recommend publication after a minor revision: A) Figure and Table captions should provide more information. The minimum is measurement parameters (e.g. on voltammetry: scan rates, times, frequency, amplitude, as appropriate) and sample composition. B) Data set was treated by statistical evaluation in the text and tables. However, error bars should be provided in Fig. 3, 6, 8. C) The English could be further polished. D) Section 4.6.2: The data should be validated using an independent method such as HPLC. At least, the authors should provide some comparison with literature: How does the time profile compare to reported pharmacokinetics of this drug?

3 Decision letter (RSOS-170324) 08-Jun-2017 Dear Dr El-wekil: Title: Development of a novel redox sensor for voltammetric determination of pantoprazole sodium during pharmacokinetic studies Manuscript ID: RSOS-170324 Thank you for submitting the above manuscript to Royal Society Open Science. On behalf of the Editors and the Royal Society of Chemistry, I am pleased to inform you that your manuscript will be accepted for publication in Royal Society Open Science subject to minor revision in accordance with the referee suggestions. Please find the reviewers' comments at the end of this email. The reviewers and handling editors have recommended publication, but also suggest some minor revisions to your manuscript. Therefore, I invite you to respond to the comments and revise your manuscript. Acknowledgements Please acknowledge anyone who contributed to the study but did not meet the authorship criteria. Please note that we cannot publish your manuscript without these end statements included (N.B. please note that there may be an error in the Data Accessibility link provided, as noted by Referee 2). We have included a screenshot example of the end statements for reference. If you feel that a given heading is not relevant to your paper, please nevertheless include the heading and explicitly state that it is not relevant to your work. Because the schedule for publication is very tight, it is a condition of publication that you submit the revised version of your manuscript within 7 days (i.e. by the 17-Jun-2017). If you do not think you will be able to meet this date please let me know immediately. To revise your manuscript, log into https://mc.manuscriptcentral.com/rsos and enter your Author Centre, where you will find your manuscript title listed under "Manuscripts with Decisions". Under "Actions," click on "Create a Revision." You will be unable to make your revisions on the originally submitted version of the manuscript. Instead, revise your manuscript and upload a new version through your Author Centre. When submitting your revised manuscript, you will be able to respond to the comments made by the referees and upload a file "Response to Referees" in "Section 6 - File Upload". You can use this to document any changes you make to the original manuscript. In order to expedite the processing of the revised manuscript, please be as specific as possible in your response to the referees. When uploading your revised files please make sure that you have: 1) A text file of the manuscript (tex, txt, rtf, docx or doc), references, tables (including captions) and figure captions. Do not upload a PDF as your "Main Document". 2) A separate electronic file of each figure (EPS or print-quality PDF preferred (either format should be produced directly from original creation package), or original software format) 3) Included a 100 word media summary of your paper when requested at submission. Please ensure you have entered correct contact details (email, institution and telephone) in your user account

4) Included the raw data to support the claims made in your paper. You can either include your data as electronic supplementary material or upload to a repository and include the relevant doi within your manuscript 5) All supplementary materials accompanying an accepted article will be treated as in their final form. Note that the Royal Society will neither edit nor typeset supplementary material and it will be hosted as provided. Please ensure that the supplementary material includes the paper details where possible (authors, article title, journal name). Supplementary files will be published alongside the paper on the journal website and posted on the online figshare repository (https://figshare.com). The heading and legend provided for each supplementary file during the submission process will be used to create the figshare page, so please ensure these are accurate and informative so that your files can be found in searches. Files on figshare will be made available approximately one week before the accompanying article so that the supplementary material can be attributed a unique DOI. Once again, thank you for submitting your manuscript to Royal Society Open Science. The chemistry content of Royal Society Open Science is published in collaboration with the Royal Society of Chemistry. I look forward to receiving your revision. If you have any questions at all, please do not hesitate to get in touch. Best wishes, Dr Siobhán Hackett Publishing Editor Royal Society of Chemistry Email: chemistryopenscience@rsc.org On behalf of the Subject Editor Dr Anthony Stace and the Associate Editor Dr Catherine Cazin. ********************************************** RSC Associate Editor: Comments to the Author: Please address all points raised by the reviewers. Submit a rebuttal letter detailing how the comments were addressed. Submit a version of the manuscript with all changes highlighted. 4 RSC Subject Editor: Comments to the Author: Although the manuscript has been accepted with minor revision, one of the referees has proposed that major changes are required before the paper can be finally accepted. Please address the comments by both referees and in a covering letter list the changes that have been made. ********************************************** Reviewer comments to Author: Reviewer: 1 Comments to the Author(s) The Comments are presented in attached file. Reviewer: 2 Comments to the Author(s) It is a very interesting study on how bromocresol green modifications of pencil electrodes improve the determination of pantoprazol. Many parameters have been studied. The sensor was

applied in challenging real samples like blood plasma, and even a pharmacokinetic study in rabbit was conducted. Analytical performance is quite impressive. The LOD of 22 nm is supported by the data. I recommend publication after a minor revision: A) Figure and Table captions should provide more information. The minimum is measurement parameters (e.g. on voltammetry: scan rates, times, frequency, amplitude, as appropriate) and sample composition. B) Data set was treated by statistical evaluation in the text and tables. However, error bars should be provided in Fig. 3, 6, 8. C) The English could be further polished. D) Section 4.6.2: The data should be validated using an independent method such as HPLC. At least, the authors should provide some comparison with literature: How does the time profile compare to reported pharmacokinetics of this drug? E) There was, some trouble with the link provided on page 16, line 6 "http://dx. doi.org/10.5061/dryad.1g98m" This link does not work. If you follow the DOI, you end up with a study titled "Data from: Modelling the impact of curtailing antibiotic usage in food animals on antibiotic resistance in humans" by van Bunnik and Woolhouse. This needs attention. 5 Author's Response to Decision Letter for (RSOS-170324) See Appendix B. Decision letter (RSOS-170324.R1) 03-Jul-2017 Dear Dr El-wekil: Title: Development of a novel redox sensor for voltammetric determination of pantoprazole sodium during pharmacokinetic studies Manuscript ID: RSOS-170324.R1 Thank you for your email. It is a pleasure to accept your manuscript in its current form for publication in Royal Society Open Science. The chemistry content of Royal Society Open Science is published in collaboration with the Royal Society of Chemistry. Thank you for your fine contribution. On behalf of the Editors of Royal Society Open Science and the Royal Society of Chemistry, I look forward to your continued contributions to the Journal. Yours sincerely, Siobhán Hackett Royal Society Open Science chemistryopenscience@rsc.org

6 On behalf of the Subject Editor Dr Anthony Stace and the Associate Editor Dr Catherine Cazin. ******** RSC Associate Editor Comments to the Author: (There are no comments.) ***************************

Appendix A Downloaded from http://rsos.royalsocietypublishing.org/ on September 14, 2018 Development of a novel redox sensor for voltammetric determination of pantoprazole sodium during pharmacokinetic studies Comments to the Authors: The paper presents an electrochemical sensor based on graphite electrode modified with poly (bromocresol green). It seems that the authors showed many interesting results. Considering the novelty of the paper, I think it might be published on Royal Society Open Science after major revision. Before accepting the paper, I recommend the authors to improve the paper as follows: 1. Why the linear range is different between Fig. 7 (15-180 10-8 M) and Table 1 (40-350x10-8 M)? The error bars should be added to calibration plot. 2. The authors evaluated the scan rate study in the range from 30 to 150 mv s -1 (Page 11, Line 6). However, the authors were obtained more results as shown in Fig. 6B. Therefore, the graph related to scan rate study in all obtained scan rate value and related regression equation should be added. 3. The deposition time and potential results for PAN analysis should be added to manuscript with an error bar. And, more discussions about deposition step should be added. 4. As seen in Table 6, Glassy carbon electrode (GCE) developed by Elsied and et. al superior analytical performance compared to proposed Poly(BGE)/PGE. Therefore,

the authors should be presented the superiority of proposed electrochemical sensor Downloaded from http://rsos.royalsocietypublishing.org/ on September 14, 2018 in terms of analytical perspective. And, the authors should check the more literatures for the detection of PAN sodium. (Journal of Pharmaceutical and Biomedical Analysis 33 (2003) 687-692; Analytical Letters, 38: 1389 1404, 2005). 5. The authors should carefully check the manuscript for English language errors.

Appendix B Dear Prof. Siobhán Hackett, We would like to thank you very much for considering our work to be published in Royal Society Open Science. Our appreciation is also extended to reviewers for their constructive comments. Please find below our point by point response. All the changes were highlighted by yellow in the revised version. Reviewer 1: 1- Why the linear range is different between Fig. 7 (15-180 10-8 M) and Table 1 (40-350x10-8 M)? The error bars should be added to calibration plot. 2-The authors evaluated the scan rate study in the range from 30 to 150 mv s -1 (Page11, Line 6). However, the authors were obtained more results as shown in Fig. 6B.Therefore, the graph related to scan rate study in all obtained scan rate value andrelated regression equation should be added. 3- The deposition time and potential results for PAN analysis should be added tomanuscript with an error bar. And, more discussions about deposition step should be added. 4- As seen in Table 6, Glassy carbon electrode (GCE) developed by Elsied and et. Alsuperior analytical performance compared to proposed Poly (BGE)/PGE. Therefore, the authors should be presented the superiority of proposed electrochemical sensor in terms of analytical perspective. And, the authors should check the more literatures for

thedetection of PAN sodium. (Journal of Pharmaceutical and Biomedical Analysis 33 (2003) 687-692; Analytical Letters, 38: 1389 1404, 2005). 5- The authors should carefully check the manuscript for English language errors. English language errors have been corrected throughout the whole manuscript. Reviewer 2: 1- Figure and Table captions should provide more information. The minimum is measurement parameters (e.g. on voltammetry: scan rates, times, frequency, amplitude, as appropriate) and sample composition. 2- Data set was treated by statistical evaluation in the text and tables. However, error bars should be provided in Fig. 3, 6, 8. 3- The English could be further polished. 4- Section 4.6.2: The data should be validated using an independent method such as HPLC. At least, the authors should provide some comparison with literature: How does the time profile compare to reported pharmacokinetics of this drug? To the best of our knowledge, the available HPLC data in the literature was for human plasma and not for rabbit plasma. 5- There was, some trouble with the link provided on page 16, line 6. Corrected.