A high-performance liquid chromatographic method with diode-array dete
ction (HPLC/DAD) for systematic toxicological analysis of human blood
or plasma samples is presented. After single-step liquid/liquid extrac
tion at pH 9.5 using chloroform/2-propanol/n-heptane (60:14:26, v/v/v)
, the drugs elute isocratically from a NovaPak C18 (Waters) 4-mu m col
umn (300 mm X 3.9 mm, i.d.) at 30 degrees C, with methanol/tetrahydrof
uran/pH 2.6 phosphate buffer (65:5:30, v/v/v) as the mobile phase (flo
w rate 0.8 mL/min). Full UV spectra from 200 to 400 nm (resolution 1.3
mm) are recorded on-line during the 20 min chromatographic run. Solut
e identification may be automatically performed by comparison of analy
tical data (retention times and UV spectra) with references of 311 pha
rmaceuticals, toxicants and drugs of abuse stored in a computerized li
brary. The method is simple, rapid, relatively inexpensive and highly
specific. The previously reported applications of HPLC/DAD technology
to drug screening are reviewed, and the interests and limitations of t
he method are discussed in the light of this literature.