Development of a sensitive LC-MS/MS method for quantification of linezolid and its primary metabolites in human serum.
J Pharm Biomed Anal
; 178: 112968, 2020 Jan 30.
Article
en En
| MEDLINE
| ID: mdl-31727360
ABSTRACT
Linezolid (LZD) is a widely used antimicrobial that is active against a broad range of disease-causing bacteria. Myelosuppression is major treatment-limiting toxicity of LZD that occurs more frequently in patients with renal insufficiency. Quantification of LZD and its two primary metabolites (PNU-142300 and PNU-142586), which undergo significant renal elimination, may support design of improved dosing strategies to mitigate the risk of myelosuppression. In this study, we established the first liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of LZD and its main metabolites in human serum. Proteins in serum samples were precipitated with acetonitrile containing a deuterated internal standard. Chromatographic separation of analytes was performed with Waters X-bridge column (C18, 150â¯×â¯4.6â¯mm, 3.5⯵m) at 25⯰C and subjected to mass analysis using positive electro-spray ionization. The mobile phase A was water with 0.1% formic acid, and mobile phase B was acetonitrile with 0.1% formic acid at a flow rate of 0.6â¯mL/min, within a 15â¯min run time. Standard curves were linear and correlation coefficients (r2) were ≥0.99 for concentration ranges of 0.1-50⯵g/mL for LZD and PNU-142300, and 0.1-25⯵g/mL for PNU-142586. The inter- and intra-assay precisions were <15% for all analytes in quality control samples, and the accuracies ranged from 97 to 112%. Extraction recoveries ranged from 78 to 103% for all analytes, and there was no significant matrix effect. Samples from 10 patients (5 with renal impairment) were assayed. Mean (SD) LZD, PNU-142300 and PNU-142586 trough concentrations were 19.4(6.8), 11.6(6.8), 25.7(16.4) µg/mL, respectively, in patients with renal impairment. These values were 2.5-, 5.8-, and 6.8-fold higher for LZD, PNU-142300 and PNU-142586, respectively compared to patients without renal impairment. The method was effectively applied in the determination of LZD and its main metabolites in human serum.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cromatografía Líquida de Alta Presión
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Espectrometría de Masas en Tándem
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Linezolid
Tipo de estudio:
Diagnostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2020
Tipo del documento:
Article