Bioanalytical method validation to quantify ketorolac in human vitreous and aqueous via surrogate matrix of human plasma

Purpose Intracameral phenylephrine 1.0%/ketorolac 0.3% (OMIDRIA®) is used during cataract surgery to prevent intraoperative miosis and reduce postoperative pain. Although studied in beagles, no human data exist showing the duration ketorolac remains in the eye postoperatively. A clinical trial measu...

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Main Authors: Prajita Pandey, Brianna A. White, Colin Goswell, Neelanjan Bose, Sara Butterworth Connell, Nicolee Schulze, Jim Nevelos, Ana Najafi, Ramin Najafi, Ryan K. Cheu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Future Science OA
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Online Access:https://www.tandfonline.com/doi/10.1080/20565623.2025.2476866
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author Prajita Pandey
Brianna A. White
Colin Goswell
Neelanjan Bose
Sara Butterworth Connell
Nicolee Schulze
Jim Nevelos
Ana Najafi
Ramin Najafi
Ryan K. Cheu
author_facet Prajita Pandey
Brianna A. White
Colin Goswell
Neelanjan Bose
Sara Butterworth Connell
Nicolee Schulze
Jim Nevelos
Ana Najafi
Ramin Najafi
Ryan K. Cheu
author_sort Prajita Pandey
collection DOAJ
description Purpose Intracameral phenylephrine 1.0%/ketorolac 0.3% (OMIDRIA®) is used during cataract surgery to prevent intraoperative miosis and reduce postoperative pain. Although studied in beagles, no human data exist showing the duration ketorolac remains in the eye postoperatively. A clinical trial measuring ketorolac concentrations in aqueous/vitreous samples necessitated the development of a validation process for acquiring these measurements. Due to limited human aqueous/vitreous humor sample availability, a bioanalytical method was developed and validated to quantify ketorolac levels using human plasma as a surrogate matrix.Methods The developed process involves extracting ketorolac and its internal standard (ketorolac-d5) from plasma as a surrogate for aqueous and vitreous humor using a protein precipitation sample preparation technique, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.Results The validated method can be successfully applied for quantitation of ketorolac over a concentration range of 2.5 ng/mL to 5000 ng/mL. The method met the acceptance criteria with respect to selectivity, specificity, precision, accuracy, linearity, dilution integrity, and stability.Conclusions The validated method can use plasma as a surrogate matrix for quantitation of ketorolac in aqueous and vitreous humor, thereby eliminating the need to procure human vitreous and aqueous samples for validation prior to initiation of a clinical trial.
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spelling doaj-art-e048fad4b10244d29d9b1246953622c42025-08-20T02:07:19ZengTaylor & Francis GroupFuture Science OA2056-56232025-12-0111110.1080/20565623.2025.2476866Bioanalytical method validation to quantify ketorolac in human vitreous and aqueous via surrogate matrix of human plasmaPrajita Pandey0Brianna A. White1Colin Goswell2Neelanjan Bose3Sara Butterworth Connell4Nicolee Schulze5Jim Nevelos6Ana Najafi7Ramin Najafi8Ryan K. Cheu9Emery Pharma, Alameda, CA, USAEmery Pharma, Alameda, CA, USAEmery Pharma, Alameda, CA, USAEmery Pharma, Alameda, CA, USARayner Group, Bellevue, WA, USARayner Group, Bellevue, WA, USARayner Group, Bellevue, WA, USAEmery Pharma, Alameda, CA, USAEmery Pharma, Alameda, CA, USAEmery Pharma, Alameda, CA, USAPurpose Intracameral phenylephrine 1.0%/ketorolac 0.3% (OMIDRIA®) is used during cataract surgery to prevent intraoperative miosis and reduce postoperative pain. Although studied in beagles, no human data exist showing the duration ketorolac remains in the eye postoperatively. A clinical trial measuring ketorolac concentrations in aqueous/vitreous samples necessitated the development of a validation process for acquiring these measurements. Due to limited human aqueous/vitreous humor sample availability, a bioanalytical method was developed and validated to quantify ketorolac levels using human plasma as a surrogate matrix.Methods The developed process involves extracting ketorolac and its internal standard (ketorolac-d5) from plasma as a surrogate for aqueous and vitreous humor using a protein precipitation sample preparation technique, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.Results The validated method can be successfully applied for quantitation of ketorolac over a concentration range of 2.5 ng/mL to 5000 ng/mL. The method met the acceptance criteria with respect to selectivity, specificity, precision, accuracy, linearity, dilution integrity, and stability.Conclusions The validated method can use plasma as a surrogate matrix for quantitation of ketorolac in aqueous and vitreous humor, thereby eliminating the need to procure human vitreous and aqueous samples for validation prior to initiation of a clinical trial.https://www.tandfonline.com/doi/10.1080/20565623.2025.2476866Surrogate matrixvalidation studyliquid chromatography-tandem mass spectrometryOMIDRIAphenylephrine/ketorolacketorolac
spellingShingle Prajita Pandey
Brianna A. White
Colin Goswell
Neelanjan Bose
Sara Butterworth Connell
Nicolee Schulze
Jim Nevelos
Ana Najafi
Ramin Najafi
Ryan K. Cheu
Bioanalytical method validation to quantify ketorolac in human vitreous and aqueous via surrogate matrix of human plasma
Future Science OA
Surrogate matrix
validation study
liquid chromatography-tandem mass spectrometry
OMIDRIA
phenylephrine/ketorolac
ketorolac
title Bioanalytical method validation to quantify ketorolac in human vitreous and aqueous via surrogate matrix of human plasma
title_full Bioanalytical method validation to quantify ketorolac in human vitreous and aqueous via surrogate matrix of human plasma
title_fullStr Bioanalytical method validation to quantify ketorolac in human vitreous and aqueous via surrogate matrix of human plasma
title_full_unstemmed Bioanalytical method validation to quantify ketorolac in human vitreous and aqueous via surrogate matrix of human plasma
title_short Bioanalytical method validation to quantify ketorolac in human vitreous and aqueous via surrogate matrix of human plasma
title_sort bioanalytical method validation to quantify ketorolac in human vitreous and aqueous via surrogate matrix of human plasma
topic Surrogate matrix
validation study
liquid chromatography-tandem mass spectrometry
OMIDRIA
phenylephrine/ketorolac
ketorolac
url https://www.tandfonline.com/doi/10.1080/20565623.2025.2476866
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