PONE-D-24-28984High Performance Liquid Chromatographic Method for Determination of Voriconazole in Pure and Gel FormulationPLOS ONE

Dear Dr. Anwar,

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Additional Editor Comments:

I am pleased to say that we are excited about the possibility of publishing your work. However, reviewers reported several concerns, mixed decisions between major revisions and rejection, and the need for major revisions in the original version of the manuscript. Please read carefully all reviewers’ reports addressing and answering all comments and suggestions. So, I kindly invite the authors to realize a thoughtful revision of the submitted manuscript to achieve publication endorsement by most reviewers. Thank you and best regards,

António Machado

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

Reviewer #4: No

Reviewer #5: No

Reviewer #6: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

Reviewer #4: No

Reviewer #5: No

Reviewer #6: No

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

Reviewer #5: Yes

Reviewer #6: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

Reviewer #4: No

Reviewer #5: No

Reviewer #6: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Following points should be confirmed again;

1. The figure number "1a" is repeated... correct the same

2. Fig 2 shows retention time 3.782 however in the text it is mentioned as 4.14 against the same figure

3. Check the unit in figure 3 ....microgram per 100 gm or ml

4. Table 2 data for theoretical plates and tailing factor and its description in the text is not matching

Reviewer #2: The current manuscript mainly focuses on determination of voriconazole in pure and gel formulation which has been already reported in various study as also mentioned in introduction section. I feel there is novelty issue.

Except that I have some observation as below:

The introduction is not well-written.

Purity of Voriconazole should be mentioned.

Preparation of Gel formulation must be supported by suitable reference.

The quality of the English language throughout the manuscript is inferior (for ex; see the section Chromatographic Condition).

The extract concentration of standard used for calibration curve preparation should be mentioned in manuscript.

The presentation of the results and discussion is not well organized.

Figure 2 & 4 looks similar.

Chemical structure should be self-drawn.

Some references are not as per journal guidelines.

Reviewer #3: The manuscript is good and clear however some comments below should be considered in the revised version.

-No literature was provided for the HPLC and its application or validation parameters selection, please use the following reference list:

#Yehia, A.M. and Mohamed, H.M., 2016. Journal of Separation Science, 39(11), pp.2114-2122.

#Yehia, A.M.,et al., 2017. Chromatographia, 80, pp.99-107.

#Yehia, A.M., et al, 2018. Separation Science Plus, 1(6), pp.395-403.

#Weshahy, S. et al, 2020. Microchemical Journal, 157, p.105047.

#Yehia, A.M., et al, 2021. Chromatographia, 84, pp.1-11.

#Yehia, A.M. and Essam, H.M., 2016. Journal of Separation Science, 39(17), pp.3357-3367.

-The final volume should be specified in the preparation of solution part.

-Technically, Liter should be abbreviated in L in ml.

-In LOD and LOQ calculation "σ" is the standard deviation of what?

-Please specify the limits in varying the flow rate (??ml/min)

-Robustness should be calculated collectively for one parameter change but not for each level within the same parameter.

-Please use reliable figure especially for the chemical structure.

Reviewer #4: PONE-D-24-28984

Authors reported High-Performance Liquid Chromatographic Method for Determination of Voriconazole in Pure and Gel Formulation, as a reviewer, I do not question the importance of the proposed work. However, a significant number of analytical methods are already published. The development presented here is not a genuinely innovative contribution and does not meet the journal's standards. It seems that the quantification of the analyte from a simple matrix and the development of new HPLC methods without specific challenges considering the principles of separation science is a contribution of little relevance to the journal's audience.

Few reported methods:

1. G. Srinubabu, Ch. A.I. Raju, N. Sarath, P. Kiran Kumar, J.V.L.N. Seshagiri Rao, Development and validation of a HPLC method for the determination of voriconazole in pharmaceutical formulation using an experimental design, Talanta, Volume 71, Issue 3, 2007, Pages 1424-1429, https://doi.org/10.1016/j.talanta.2006.04.042.

2. Khetre AB, Sinha PK, Damle MC, Mehendre R. Development and Validation of Stability Indicating RP-HPLC Method for Voriconazole. Indian J Pharm Sci. 2009 Sep;71(5):509-14. doi: 10.4103/0250-474X.58178. PMID: 20502568; PMCID: PMC2866341.

3. Sahar Yousefian, Farzaneh Dastan, Majid Marjani, Payam Tabarsi, Saghar Barati, Nahid Shahsavari, Farzad Kobarfard. Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis https://doi.org/10.1155/2021/5497427

4. Yasu, T.; Nomura, Y.; Gando, Y.; Matsumoto, Y.; Sugita, T.; Kosugi, N.; Kobayashi, M. High-Performance Liquid Chromatography for Ultra-Simple Determination of Plasma Voriconazole Concentration. J. Fungi 2022, 8, 1035. https://doi.org/10.3390/jof8101035

5. Zhang M, Moore GA, Barclay ML, Begg EJ. 2013. A Simple High-Performance Liquid Chromatography Method for Simultaneous Determination of Three Triazole Antifungals in Human Plasma. Antimicrob Agents Chemother 57:. https://doi.org/10.1128/aac.00768-12

Then, based on the above observations, my overall recommendation is to reject the manuscript in its present form.

Reviewer #5: I strongly recommend rejecting the manuscript considering missing novelty in the manuscript. There are so many reported methods available on determination of Voriconazole. Few of them are mentioned below for your reference:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866341/

https://dergipark.org.tr/tr/download/article-file/166318

https://www.sciencedirect.com/science/article/abs/pii/S0039914007000021

Reviewer #6: The research paper details the development and validation of an RP-HPLC method for determining Voriconazole (VZ) in both pure and gel formulations. The method is described as quick, accurate, and robust, with good precision and a short retention time. However, the novelty of the work is questionable. RP-HPLC is a well-established technique for the analysis of Voriconazole, as evidenced by the numerous previous studies referenced in the introduction. The paper does not clearly distinguish how this method significantly improves upon or differs from existing methods. However, without clear evidence or comparison showing that this method significantly overcomes these limitations, the rationale lacks full support. The application to gel formulations is a reasonable extension, though this aspect alone does not establish strong novelty. Although the short retention time and the method’s application to gel formulations are positive features, these aspects alone do not constitute substantial innovation, especially without a direct comparison to other methods in terms of time, cost, or sensitivity.

Strengths:

1. Comprehensive Validation: The method is thoroughly validated according to ICH guidelines, covering system suitability, linearity, accuracy, precision, specificity, and robustness.

2. Short Retention Time: A retention time of less than 4 minutes is efficient for routine analysis.

3. Application to Gel Formulations: The method’s successful application to both pure and gel formulations broadens its utility.

Areas for Improvement:

1. Comparative Analysis for Novelty: To better demonstrate novelty, the paper should include a comparison with existing RP-HPLC methods, particularly highlighting specific improvements in terms of time, cost, simplicity, or sensitivity.

2. Detailed Method Development Justification: The paper could benefit from a more detailed explanation of the choice of mobile phase composition, flow rate, and other chromatographic conditions, perhaps by comparing these with those used in similar studies.

3. Robustness Testing: While the method's robustness is addressed, the paper should detail the exact parameters tested and their impact on the analysis, along with statistical data to support the findings.

4. Discussion on Specificity and Degradation Studies: The discussion of degradation studies and the method's specificity could be enhanced with more detailed results and interpretations, particularly in the context of forced degradation.

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Reviewer #1: Yes: Dinesh Rishipathak

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

Reviewer #5: No

Reviewer #6: No

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Attachments

Attachment

Submitted filename: review comments.docx

High Performance Liquid Chromatographic Method for Determination of Voriconazole in Pure and Gel Formulation

PONE-D-24-28984R1

Dear authors,

I am pleased to inform you that both reviewers enjoyed the manuscript very much and endorsed the revised manuscript for publication. Please try to briefly enhance the novelty of the work during the process editorial process as recommended by Reviewer 6.

Thank you for choosing Plos ONE journal to publish your study.

Best regards,

António Machado

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #6: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #6: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #6: No

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #6: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #6: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #3: All comments have been addressed in the revised version and the work is now suitable for publication. No conflict of dual publication or research ethics.

Reviewer #6: What is Novelty of your published method in terms of sensitivity, mobile phase, retention time etc.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: No

Reviewer #6: No

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