PONE-D-19-17238

Development and Validation of LC-MS/MS Method for Imatinib and Norimatinib Monitoring by Finger-prick DBS in Gastrointestinal Stromal Tumor Patients

PLOS ONE

Dear Dr. Posocco,

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John Matthew Koomen, PhD

Academic Editor

PLOS ONE

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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: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

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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: Yes

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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: Minor editing for English grammar and usage. Line 104 should have a reference. Which model Millipore was used to produce water in line 135. Working solutions and calibrators are claimed to be made "from A to L", however only ten working solutions and calibrators were identified (Lines 150, 152, 161 & 163). Line 345 states that the clinical protocol was designed to collect blood "without anticoagulant", however lines 319 & 320 state that in the clinical protocol, venous blood was collected with K-EDTA, an anti-coagulant. Was a separate vacutainer collected for the correlation between finger prick and venous collection? Line 505, indicate "LCCC" stands for Lin’s Concordance Correlation Coefficient. Typo on Line 542 "LC-M/MS"

Reviewer #2: I think the article is well written in a straightforward manner, thus easy to follow by the readers. The validation experiments done by the authors are comprehensive and sufficient.

There are only a few minor revisions/addendum:

L152, 159-163: There is some error in listing of quality control concentrations, the final concentrations do not add up from the working concentrations. It is suggested to keep the order of concentrations consistent, best listed in an ascending manner.

L301-304: The HPLC parameters changed from the method development (L186-189) to the plasma sample analysis. Please discuss why it has changed and the effects it brought. Normally, the method validated should be kept the same in GLP conditions.

L449: change “follow” to “follows”

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Reviewer #1: Yes: Samer Sansil

Reviewer #2: No

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Development and Validation of LC-MS/MS Method for Imatinib and Norimatinib Monitoring by Finger-prick DBS in Gastrointestinal Stromal Tumor Patients

PONE-D-19-17238R1

Dear Dr. Posocco,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

John Matthew Koomen, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #2: 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 #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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 #2: Yes

**********

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 #2: Yes

**********

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: Thank you for addressing my comments. You are correct that Line 373 already states the abbreviation and thus, does not need to be repeated. The change does make it easier for the reader.

Reviewer #2: The authors have addressed the reviewers' concerns satisfactorily and in my opinion, should proceed for acceptance.

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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: Yes: Samer Sansil

Reviewer #2: No