Quantification of rifampicin in human plasma and cerebrospinal fluid by a highly sensitive and rapid liquid chromatographic-tandem mass spectrometric method

J Pharm Biomed Anal. 2012 Nov;70(6):523-8. doi: 10.1016/j.jpba.2012.05.028. Epub 2012 Jun 1.

Abstract

A highly sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed to measure the levels of the antitubercular drug rifampicin (RIF) in human plasma and cerebrospinal fluid (CSF). The analyte and internal standard (IS) were isolated from plasma and CSF by a simple organic solvent based precipitation of proteins followed by centrifugation. Detection was carried out by electrospray positive ionization mass spectrometry in the multiple-reaction monitoring (MRM) mode. The assay was linear in the concentration range 25-6400 ng/mL with intra- and inter-day precision of <7% and <8%, respectively. The validated method was applied to the study of RIF pharmacokinetics in human CSF and plasma over 25 h period after a 10 mg/kg oral dose.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Administration, Oral
  • Antibiotics, Antitubercular / administration & dosage
  • Antibiotics, Antitubercular / blood*
  • Antibiotics, Antitubercular / cerebrospinal fluid*
  • Antibiotics, Antitubercular / pharmacokinetics
  • Area Under Curve
  • Calibration
  • Centrifugation
  • Chemical Precipitation
  • Chromatography, High Pressure Liquid* / standards
  • Half-Life
  • Humans
  • Limit of Detection
  • Linear Models
  • Metabolic Clearance Rate
  • Models, Biological
  • Reference Standards
  • Reproducibility of Results
  • Rifampin / administration & dosage
  • Rifampin / blood*
  • Rifampin / cerebrospinal fluid*
  • Rifampin / pharmacokinetics
  • Sensitivity and Specificity
  • Solvents / chemistry
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry* / standards

Substances

  • Antibiotics, Antitubercular
  • Solvents
  • Rifampin