Lorazepam analysis using liquid chromatography: improved sensitivity for single-dose pharmacokinetic studies.

Analytical methodology for lorazepam in body fluids has been hampered by the extremely high sensitivity required for detection of the low plasma lorazepam concentrations achieved after usual therapeutic dose as well as by thermal instability of the 3-hydroxybenzodiazepine ring, making gas chromatographic methods difficult to standardize. High-performance liquid chromatographic (HPLC) methods are available for determination of benzodiazepine concentrations in human plasma [l51, but none are sensitive enough to measure the low plasma lorazepam concentrations attained during single-dose pharmacokinetic studies. Gasliquid chromatography using electron-capture detection (GLC-ECD) has been used with greater sensitivity; however, this methodology requires the use of another 3-hydroxybenzodiazepine as internal standard and the assumption that thermal molecular rearrangement on-column occurs to the same extent with lorazepam and internal standard [ 61. Here we present a liquid chromatographic method, comparable in sensitivity to the GLC-ECD method, for analysis of lorazepam after single therapeutic doses. Application of this method to the pharmacokinetic study of lorazepam in a healthy male volunteer is presented. The method is then compared to the GLC-ECD method [ 6 J .