Your browser doesn't support javascript.
loading
A battery of tandem mass spectrometry assays with stable isotope-dilution for the quantification of 15 anti-tuberculosis drugs and two metabolites in patients with susceptible-, multidrug-resistant- and extensively drug-resistant tuberculosis.
Mercier, T; Desfontaine, V; Cruchon, S; Da Silva Pereira Clara, J A; Briki, M; Mazza-Stalder, J; Kajkus, A; Burger, R; Suttels, V; Buclin, T; Opota, O; Koehler, N; Sanchez Carballo, P M; Lange, C; André, P; Decosterd, L A; Choong, E.
Afiliação
  • Mercier T; Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Desfontaine V; Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Cruchon S; Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Da Silva Pereira Clara JA; Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Briki M; Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Mazza-Stalder J; Service of Pulmology, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Kajkus A; Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Burger R; Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Division of Intensive Care, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Suttels V; Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Buclin T; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Opota O; Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Koehler N; Clinical Infectious Diseases Research Center Borstel, Germany, German Center for Infection Research (DZIF), University of Lübeck, Lübeck, Germany.
  • Sanchez Carballo PM; Clinical Infectious Diseases Research Center Borstel, Germany, German Center for Infection Research (DZIF), University of Lübeck, Lübeck, Germany.
  • Lange C; Clinical Infectious Diseases Research Center Borstel, Germany, German Center for Infection Research (DZIF), University of Lübeck, Lübeck, Germany; Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany; Baylor College of Medicine and Texas Childrens Hospital, Houston,
  • André P; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Decosterd LA; Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Choong E; Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. Electronic address:
J Chromatogr B Analyt Technol Biomed Life Sci ; 1211: 123456, 2022 Nov 15.
Article em En | MEDLINE | ID: mdl-36240540
ABSTRACT

OBJECTIVE:

Anti-tuberculosis (antiTB) drugs are characterized by an important inter-interindividual pharmacokinetic variability poorly predictable from individual patients' characteristics. Therapeutic drug monitoring (TDM) may therefore be beneficial for patients with Mycobacterium tuberculosis infection, especially for the management of multidrug/extensively drug resistant- (MDR/XDR)-TB. Our objective was to develop robust HPLC-MS/MS methods for plasma quantification of 15 antiTB drugs and 2 metabolites, namely rifampicin, isoniazid plus N-acetyl-isoniazid, pyrazinamide, ethambutol (the conventional quadritherapy for susceptible TB) as well as combination of agents against MDR/XDR-TB bedaquiline, clofazimine, delamanid and its metabolite M1, levofloxacin, linezolid, moxifloxacin, pretomanid, rifabutin, rifapentine, sutezolid, and cycloserine.

METHODS:

Plasma protein precipitation was used for all analytes except cycloserine, which was analyzed separately after derivatization with benzoyl chloride. AntiTB quadritherapy drugs (Pool1) were separated by Hydrophilic Interaction Liquid Chromatography (column Xbridge BEH Amide, 2.1 × 150 mm, 2.5 µm, Waters®) while MDR/XDR-TB agents (Pool 2) and cycloserine (as benzoyl derivative) were analyzed by reverse phase chromatography on a column XSelect HSS T3, 2.1 × 75 mm, 3.5 µm (Waters®). All runs last <7 min. Quantification was performed by selected reaction monitoring electrospray tandem mass spectrometry, using stable isotopically labelled internal standards.

RESULTS:

The method covers the clinically relevant plasma levels and was extensively validated based on FDA recommendations, with intra- and inter-assay precision (CV) < 15% over the validated ranges. Application of the method is illustrated by examples of TDM for two patients treated for drug-susceptible- and MDR-TB.

CONCLUSION:

Such convenient extraction methods and the use of stable isotope-labelled drugs as internal standards provide an accurate and precise quantification of plasma concentrations of all major clinically-used antiTB drugs regimens and is optimally suited for clinically efficient TDM against tuberculosis.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tuberculose Resistente a Múltiplos Medicamentos / Tuberculose Extensivamente Resistente a Medicamentos / Mycobacterium tuberculosis Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tuberculose Resistente a Múltiplos Medicamentos / Tuberculose Extensivamente Resistente a Medicamentos / Mycobacterium tuberculosis Idioma: En Ano de publicação: 2022 Tipo de documento: Article