Rapid and highly sensitive quantification of the anti-tuberculosis agents isoniazid, ethambutol, pyrazinamide, rifampicin and rifabutin in human plasma by UPLC-MS/MS.
J Pharm Biomed Anal
; 180: 113076, 2020 Feb 20.
Article
en En
| MEDLINE
| ID: mdl-31896523
ABSTRACT
With the increased cases of multidrug- or rifampicin-resistant tuberculosis and co-infection with HIV globally, it is difficult to achieve ideal clinical responses because of poor drug absorption and drug-drug interactions. Herein, a bioanalytical UPLC-MS/MS method was developed and validated to quantify five anti-TB agents in human plasma samples for detecting blood drug concentrations to improve therapeutic effects. To overcome the matrix effects, stable isotope labeled analogue of each analyte was used for internal standardization. A simple single-step protein precipitation by acetonitrile was employed for the sample preparation, then the analytes including rifampicin, rifabutin, pyrazinamid, ethambutol, isoniazid and their isotope labeled internal standards (ILISs) were implemented on an HILIC silica column with a gradient mode. The linear range for each analyte was covering the peak drug concentration (Cmax) in the 20 times diluted plasma samples. The coefficient of variation of intra- and inter-day precision was less than 17.0 %, and the accuracy ranged between 91.5 and 110.0 %. The extraction recoveries of all agents were ≥90.2 %, and the matrix effects with internal standard-normalization for all agents were 97.1-110.0 %. The optimal blood sampling time was designed basing on the results of stability validation. This UPLC-MS/MS method with a run time of 3.5â¯min was successfully applied to routine therapeutic monitoring of the five anti-TB agents in patient plasma.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirazinamida
/
Rifampin
/
Monitoreo de Drogas
/
Rifabutina
/
Etambutol
/
Isoniazida
/
Antituberculosos
Tipo de estudio:
Diagnostic_studies
/
Guideline
Límite:
Humans
Idioma:
En
Revista:
J Pharm Biomed Anal
Año:
2020
Tipo del documento:
Article
País de afiliación:
Puerto Rico