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Development and Validation of Analytical Method for SH-1242 in the Rat and Mouse Plasma by Liquid Chromatography/Tandem Mass Spectrometry

SH-1242, a novel inhibitor of heat shock protein 90 (HSP90), is a synthetic analog of deguelin: It was previously reported that the treatment of SH-1242 led to a strong suppression of hypoxia-mediated retinal neovascularization and vascular leakage in diabetic retinas by inhibiting the hypoxia-induc...

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Autores principales: Jeong, Yoo-Seong, Baek, Minjeong, Lee, Seungbeom, Kim, Min-Soo, Maeng, Han-Joo, Lee, Jong-Hwa, Suh, Young-Ger, Chung, Suk-Jae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037321/
https://www.ncbi.nlm.nih.gov/pubmed/31991809
http://dx.doi.org/10.3390/molecules25030531
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author Jeong, Yoo-Seong
Baek, Minjeong
Lee, Seungbeom
Kim, Min-Soo
Maeng, Han-Joo
Lee, Jong-Hwa
Suh, Young-Ger
Chung, Suk-Jae
author_facet Jeong, Yoo-Seong
Baek, Minjeong
Lee, Seungbeom
Kim, Min-Soo
Maeng, Han-Joo
Lee, Jong-Hwa
Suh, Young-Ger
Chung, Suk-Jae
author_sort Jeong, Yoo-Seong
collection PubMed
description SH-1242, a novel inhibitor of heat shock protein 90 (HSP90), is a synthetic analog of deguelin: It was previously reported that the treatment of SH-1242 led to a strong suppression of hypoxia-mediated retinal neovascularization and vascular leakage in diabetic retinas by inhibiting the hypoxia-induced upregulation of expression in hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). In this study, an analytical method for the quantification of SH-1242 in biological samples from rats and mice was developed/validated for application in pharmacokinetic studies. SH-1242 and deguelin, an internal standard of the assay, in plasma samples from the rodents were extracted with methanol containing 0.1% formic acid and analyzed at m/z transition values of 368.9→151.0 and 395.0→213.0, respectively. The method was validated in terms of accuracy, precision, dilution, matrix effects, recovery, and stability and shown to comply with validation guidelines when it was used in the concentration ranges of 1–1000 ng/mL for rat plasma and of 2–1000 ng/mL for mouse plasma. SH-1242 levels in plasma samples were readily determined using the developed method for up to 480 min after the intravenous administration of 0.1 mg/kg SH-1242 to rats and for up to 120 min to mice. These findings suggested that the current method was practical and reliable for pharmacokinetic studies on SH-1242 in preclinical animal species.
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spelling pubmed-70373212020-03-11 Development and Validation of Analytical Method for SH-1242 in the Rat and Mouse Plasma by Liquid Chromatography/Tandem Mass Spectrometry Jeong, Yoo-Seong Baek, Minjeong Lee, Seungbeom Kim, Min-Soo Maeng, Han-Joo Lee, Jong-Hwa Suh, Young-Ger Chung, Suk-Jae Molecules Article SH-1242, a novel inhibitor of heat shock protein 90 (HSP90), is a synthetic analog of deguelin: It was previously reported that the treatment of SH-1242 led to a strong suppression of hypoxia-mediated retinal neovascularization and vascular leakage in diabetic retinas by inhibiting the hypoxia-induced upregulation of expression in hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). In this study, an analytical method for the quantification of SH-1242 in biological samples from rats and mice was developed/validated for application in pharmacokinetic studies. SH-1242 and deguelin, an internal standard of the assay, in plasma samples from the rodents were extracted with methanol containing 0.1% formic acid and analyzed at m/z transition values of 368.9→151.0 and 395.0→213.0, respectively. The method was validated in terms of accuracy, precision, dilution, matrix effects, recovery, and stability and shown to comply with validation guidelines when it was used in the concentration ranges of 1–1000 ng/mL for rat plasma and of 2–1000 ng/mL for mouse plasma. SH-1242 levels in plasma samples were readily determined using the developed method for up to 480 min after the intravenous administration of 0.1 mg/kg SH-1242 to rats and for up to 120 min to mice. These findings suggested that the current method was practical and reliable for pharmacokinetic studies on SH-1242 in preclinical animal species. MDPI 2020-01-25 /pmc/articles/PMC7037321/ /pubmed/31991809 http://dx.doi.org/10.3390/molecules25030531 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jeong, Yoo-Seong
Baek, Minjeong
Lee, Seungbeom
Kim, Min-Soo
Maeng, Han-Joo
Lee, Jong-Hwa
Suh, Young-Ger
Chung, Suk-Jae
Development and Validation of Analytical Method for SH-1242 in the Rat and Mouse Plasma by Liquid Chromatography/Tandem Mass Spectrometry
title Development and Validation of Analytical Method for SH-1242 in the Rat and Mouse Plasma by Liquid Chromatography/Tandem Mass Spectrometry
title_full Development and Validation of Analytical Method for SH-1242 in the Rat and Mouse Plasma by Liquid Chromatography/Tandem Mass Spectrometry
title_fullStr Development and Validation of Analytical Method for SH-1242 in the Rat and Mouse Plasma by Liquid Chromatography/Tandem Mass Spectrometry
title_full_unstemmed Development and Validation of Analytical Method for SH-1242 in the Rat and Mouse Plasma by Liquid Chromatography/Tandem Mass Spectrometry
title_short Development and Validation of Analytical Method for SH-1242 in the Rat and Mouse Plasma by Liquid Chromatography/Tandem Mass Spectrometry
title_sort development and validation of analytical method for sh-1242 in the rat and mouse plasma by liquid chromatography/tandem mass spectrometry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037321/
https://www.ncbi.nlm.nih.gov/pubmed/31991809
http://dx.doi.org/10.3390/molecules25030531
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