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.
Highlights
Tuberculosis (TB) is one of the most important human bacterial diseases caused by mycobacterium tuberculosis (MTB) commonly affecting the lungs [1]
Several analytical methods are already available for the determination of RIF in biological fluids and pharmaceutical dosage forms, including methods based on HPTLC [7], HPLC [8,9,10,11,12,13,14,15,16], HPLC following SPE [17] or SBSE [18], UPLC [19], LC–MS/MS [20,21,22,23] and MALDI–TOF [24]
2.6.7. % recovery and matrix effect Recovery was determined by comparing the area under the curve (AUC) of extracted quality control (QC) samples (LQC, MQC and HQC) with direct injection of extracted blank plasma spiked with the same nominal concentration of RIF as in the QC samples
Summary
Tuberculosis (TB) is one of the most important human bacterial diseases caused by mycobacterium tuberculosis (MTB) commonly affecting the lungs [1]. It is an aggressive disease with one third of the World’s population reportedly being infected with MTB [1,2]. It is more common in developing countries, with more than half of the reported cases occurring in Asia [1]. In order to address these questions there is a need for a suitably selective and sensitive analytical method that is capable of measuring the drug in biological fluids.
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