Monitoring of tricyclic antidepressants in human serum and plasma by HPLC:characterization of a simple, laboratory developed method via external quality assessment
R. Theurillat et W. Thormann, Monitoring of tricyclic antidepressants in human serum and plasma by HPLC:characterization of a simple, laboratory developed method via external quality assessment, J PHARM B, 18(4-5), 1998, pp. 751-760
A reversed-phase high performance liquid chromatography (HPLC) method for t
he determination of plasma and serum levels of amitriptyline (AMI), nortrip
tyline (NORT), imipramine (IMI), desipramine (DESI), clomipramine (CLOMI),
and norclomipramine (NCLOMI) is described. The assay is based upon single s
tep liquid/liquid extraction of these compounds using hexane at pH 11 (reco
very between 92 and 105%), a Nova-Pack C-18 HPLC cartridge column, a mobile
phase composed of a phosphate buffer with 50% (v/v) acetonitrile and about
0.2% (v/v) diethylamine (final pH: 8) and solute detection at 242 nm. Usin
g 1 mi of plasma or serum and econazole as internal standard, drug levels b
etween 20 and 400 ng ml(-1) (about 60-1450 nM) were found to provide linear
calibration graphs. For drug concentrations in the range of 70-120 ng ml(-
1) (about 240-430 nM), intraday and interday imprecisions (n = 5) were dete
rmined to be < 6.0, and < 15%, respectively. Data reported include those ga
thered over a 3-year period during which this assay was employed for therap
eutic drug monitoring and clinical toxicology. The performance of the labor
atory developed assay was assessed. via analysis of monthly samples provide
d by an external quality control scheme. (C) 1998 Elsevier Science B.V. All
rights reserved.