A Systematic Approach for the Simultaneous Assay of Some Antituberculous Drugs in CSF and Plasma by Liquid Chromatography

The rationale behind the measurement of anti-tuberculous (Anti-TB) drugs in biological fluids, especially in the management of tuberculous meningitis (TBM), has been briefly discussed. A short review on methods available for laboratory use has been presented. Finally a systematic approach using liquid chromatography (LC) is presented for consideration. This approach involves a preliminary organic solvent extraction of pyrazinamide (PZA) and rifampicin (RIF) and its 25-desacetyl metabolite, 25-DRIF, from cerebrospinal fluid (CSF) or plasma samples. The drugs and their internal standards are separated on a RPB precolumn linked to a μBondapak cartridge in a Zmodule by a gradient solvent program which delivers 6% to 48% v/v of acetonitrile in a phosphate buffer (10 mM KH2PO4 pH3.5) in 10 min at 1.5 ml/min. The eluate is detected at 215 nm. This LC system can also resolve 2 other anti-TB drugs (isoniazid and p-aminosalicylic acid). Patients with TBM were treated with various combinations of anti-TB drugs and their CSF and serum samples were assayed.