Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model

Guang Yang,1,2 Yisong Yan,1,3 Jun Mao,1 Huiping Liu,1 Mingtao Chen,1 Na Zhang,1 Yaowen Li,1 Jiangjun Gu,2 Xiaohui Huang1 1Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Pharmacy, The Third People’s...

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Autores principales:	Yang G, Yan Y, Mao J, Liu H, Chen M, Zhang N, Li Y, Gu J, Huang X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	linezolid hplc-uv pk/pd model resistance Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/5608a89f24a445518149e5e07840a5c7
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spelling	oai:doaj.org-article:5608a89f24a445518149e5e07840a5c72021-11-30T18:50:36ZDevelopment and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model1178-6973https://doaj.org/article/5608a89f24a445518149e5e07840a5c72021-12-01T00:00:00Zhttps://www.dovepress.com/development-and-validation-of-an-hplc-uv-method-for-quantitation-of-li-peer-reviewed-fulltext-article-IDRhttps://doaj.org/toc/1178-6973Guang Yang,1,2 Yisong Yan,1,3 Jun Mao,1 Huiping Liu,1 Mingtao Chen,1 Na Zhang,1 Yaowen Li,1 Jiangjun Gu,2 Xiaohui Huang1 1Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Pharmacy, The Third People’s Hospital of Tongling, Tongling, Anhui, People’s Republic of China; 3Department of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, Anhui, People’s Republic of ChinaCorrespondence: Xiaohui HuangDepartment of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Meishan Road 81#, Hefei, Anhui, 230032, People’s Republic of ChinaTel +86 138 5518 3138Email math2088@163.comBackground: Linezolid (LNZ), an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens. The in vitro PK/PD model was developed based on concentrations obtained with routine doses in humans can be used to guide dose optimization in the clinic.Methods: In this study, we employed an in vitro PK/PD model to simulate the changes in the plasma concentration of linezolid in the human body against a clinical isolate of MRSA in vitro. A high-performance liquid chromatography (HPLC)-UV method was applied to measure the concentration of linezolid. Bacterial samples were collected at different times from the central compartment for count.Results: The chromatographic separation was carried out with an AichromBond-AQC18 column(250mm× 4.6mm, 5μm), using a mobile phase of water with 0.1% formic acid:acetonitrile 70:30 (v/v), followed by detection at 254 nm, and a single detection run was completed within 10 min. The method was validated by estimating the precision and accuracy for the inter- and intra-day analyses in the concentration range of 0.25– 32 mg/L. The method was linear over the investigated range of 0.125– 32 mg/L, with all correlation coef&filig;cients R2 = 0.9999. The intra-day and inter-day precisions were within 7.598%, and the method recovery ranged from 90.912% to 106.459%. In vitro PK/PD model, both the absorption and elimination of linezolid being simulated can be precisely controlled by computer. In the control group, the bacterial reached 7.9 Log10CFU/mL in the &filig;rst 48h and maintained until the end, indicating that the colonies grew well in vitro PK/PD model. In the linezolid 600 mg q12h administration group, the colony decreased to 2.39 Log10CFU/mL at 24h, showing a good bactericidal effect; however, the colonies resumed growth to the initial level in 48h, indicating an emergence of resistance.Conclusion: We successfully established an in vitro infection PK/PD model and developed an HPLC-UV method to determine linezolid concentration for resistance investigation. The results suggest that the 600 mg q12h dosing regimen may no longer be applicable and requires optimization.Keywords: linezolid, HPLC-UV, PK/PD model, resistanceYang GYan YMao JLiu HChen MZhang NLi YGu JHuang XDove Medical Pressarticlelinezolidhplc-uvpk/pd modelresistanceInfectious and parasitic diseasesRC109-216ENInfection and Drug Resistance, Vol Volume 14, Pp 5089-5098 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	linezolid hplc-uv pk/pd model resistance Infectious and parasitic diseases RC109-216
spellingShingle	linezolid hplc-uv pk/pd model resistance Infectious and parasitic diseases RC109-216 Yang G Yan Y Mao J Liu H Chen M Zhang N Li Y Gu J Huang X Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model
description	Guang Yang,1,2 Yisong Yan,1,3 Jun Mao,1 Huiping Liu,1 Mingtao Chen,1 Na Zhang,1 Yaowen Li,1 Jiangjun Gu,2 Xiaohui Huang1 1Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Pharmacy, The Third People’s Hospital of Tongling, Tongling, Anhui, People’s Republic of China; 3Department of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, Anhui, People’s Republic of ChinaCorrespondence: Xiaohui HuangDepartment of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Meishan Road 81#, Hefei, Anhui, 230032, People’s Republic of ChinaTel +86 138 5518 3138Email math2088@163.comBackground: Linezolid (LNZ), an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens. The in vitro PK/PD model was developed based on concentrations obtained with routine doses in humans can be used to guide dose optimization in the clinic.Methods: In this study, we employed an in vitro PK/PD model to simulate the changes in the plasma concentration of linezolid in the human body against a clinical isolate of MRSA in vitro. A high-performance liquid chromatography (HPLC)-UV method was applied to measure the concentration of linezolid. Bacterial samples were collected at different times from the central compartment for count.Results: The chromatographic separation was carried out with an AichromBond-AQC18 column(250mm× 4.6mm, 5μm), using a mobile phase of water with 0.1% formic acid:acetonitrile 70:30 (v/v), followed by detection at 254 nm, and a single detection run was completed within 10 min. The method was validated by estimating the precision and accuracy for the inter- and intra-day analyses in the concentration range of 0.25– 32 mg/L. The method was linear over the investigated range of 0.125– 32 mg/L, with all correlation coef&filig;cients R2 = 0.9999. The intra-day and inter-day precisions were within 7.598%, and the method recovery ranged from 90.912% to 106.459%. In vitro PK/PD model, both the absorption and elimination of linezolid being simulated can be precisely controlled by computer. In the control group, the bacterial reached 7.9 Log10CFU/mL in the &filig;rst 48h and maintained until the end, indicating that the colonies grew well in vitro PK/PD model. In the linezolid 600 mg q12h administration group, the colony decreased to 2.39 Log10CFU/mL at 24h, showing a good bactericidal effect; however, the colonies resumed growth to the initial level in 48h, indicating an emergence of resistance.Conclusion: We successfully established an in vitro infection PK/PD model and developed an HPLC-UV method to determine linezolid concentration for resistance investigation. The results suggest that the 600 mg q12h dosing regimen may no longer be applicable and requires optimization.Keywords: linezolid, HPLC-UV, PK/PD model, resistance
format	article
author	Yang G Yan Y Mao J Liu H Chen M Zhang N Li Y Gu J Huang X
author_facet	Yang G Yan Y Mao J Liu H Chen M Zhang N Li Y Gu J Huang X
author_sort	Yang G
title	Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model
title_short	Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model
title_full	Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model
title_fullStr	Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model
title_full_unstemmed	Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model
title_sort	development and validation of an hplc-uv method for quantitation of linezolid: application to resistance study using in vitro pk/pd model
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/5608a89f24a445518149e5e07840a5c7
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Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model

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