Recently, ultrahigh pressure liquid chromatography (UHPLC) has been shown t
o overcome the pressure limitations that small particles impose on conventi
onal pumping systems. High speed separations in UHPLC produce peak widths t
hat range between 100 to 1000 ms, of which many are too narrow to be monito
red by scanning mass spectrometers. The only mass spectrometer that is fast
enough for such separations is the time-of-flight mass spectrometer (TOFMS
). State-of-the-art TOFMS instruments for liquid chromatography can record
and store complete mass spectra at rates as high as 100 spectra s(-1). In t
his study, high speed separations with high resolution were demonstrated us
ing 13-15 cm X 29-100 mum i.d. capillaries packed with 1.5 mum nonporous oc
tadecylsilane- and isohesylsilane-modified silica particles utilizing a hom
e-built UHPLC system. The UPIPLC system was successfully coupled to TOFMS v
ia a liquid-sheath electrospray interface. Separations of selected combinat
orial chemistry samples, pharmaceutical compounds, and herbicides were comp
leted in less than 100 s using UHPLC/TOFMS. Total column efficiencies range
d from 20,000-30,000 plates. The fundamental and practical aspects of UHPLC
/TOFMS are discussed. Results are compared with those obtained from typical
capillary LC. (C) 2000 John Wiley & Sons, Inc.