CAPILLARY GC DETERMINATION OF FENTANYL AND MIDAZOLAM IN HUMAN PLASMA

A capillary GC method is described for simultaneously measuring fentan yl and midazolam in human plasma. Plasma was extracted at basic pH wit h cyclohexane-isopentanol (197:3) with Ro21-2212 added as internal sta ndard and fentanyl derivative as carrier. The drug was back-extracted in H2SO4 and then the extract was made basic and reextracted with hexa ne. The organic phase was evaporated at 40 degrees C under N-2 and the residue was dissolved in ethanol. A portion was analyzed on a wide-bo re capillary column (10 m x 0.53 mm) of HP-1 (2.65 mu m), operated at 255 degrees C with N-2 as carrier gas and N-P detector. The calibratio n graph for fentanyl and midazolam was linear within the respective ra nges of 0.5-100 and 5-1000 ng/ml with a correlation coefficient of 0.9 998. The recovery of fentanyl and midazolam was 99.5 +/- 4.5 and 99.9 +/- 3.2%. The coefficient of variation within a run and between runs w as less than 7%. The detection limit for fentanyl was 0.2 ng/ml plasma , and for midazolam was 0.5 ng/ml plasma. The method was applied to th erapeutic drug monitoring and pharmacokinetic studies. 1996 Academic P ress, Inc. (C) 1996 Academic Press, Inc