THERAPEUTIC GAMMA-HYDROXYBUTYRIC ACID MONITORING IN PLASMA AND URINE BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

A gas chromatographic-mass spectrometric (GC-MS) method for the determ ination of therapeutic levels of gamma-hydroxybutyric acid (GHB) in pl asma and urine samples is described. GHB is converted to its lactonic form gamma-butyrolactone (GBL) which is extracted from biological flui ds after the addition of the internal standard delta-valerolactone. Fi nal GC-MS analysis is obtained under electron impact selected ion moni toring (SIM) conditions. Mean relative recoveries of GHB from plasma a nd urine are 75.5% (RSD% = 2.2) and 76.4% (RSD% = 2.4), respectively. The assay is linear over a plasma GHB range of 2-200 mug ml-1 (r = 0.9 99) and a urine GHB range of 2-150 mug ml-1 (r = 0.998). Intra- and in ter-assay relative standard deviations (n = 5) determined at 10 and 10 0 mug ml-1 are below 5%. The method is simple, specific and accurate, and may be applied for analytical purposes related to pharmacokinetic studies and therapeutic drug monitoring.