In 1997, in an article that appeared in what then was LCGC International (now LCGC Europe), I departed from my usual technical writing, which up to then had been primarily for peer review. The LCGC editor had requested help recognizing the publication's 10th anniversary. Mass spectrometry (MS) and liquid chromatography–mass
spectrometry (LC–MS) in particular, given the rapidly evolving commercial landscape, I thought made investigating the phenomenon
worthwhile. Little did I realize how much effort a writer must devote to developing and presenting ideas in finished form.
I must have forgotten that lesson when, five years later, I agreed to write the "MS — The Practical Art" regularly.
Nearly 35 bimonthly columns later, I happened across that initial article, "Commercialization of LC–MS 1987–1997: A Successful
Decade in Review" [LCGC International, 10(11), 728–737 (1997)]. It made me curious about just how many technological advances the field of MS had witnessed during
the ensuing decade and what had not changed.
Of course, the technological basis, or history, remains unchanged for what was then called the "hyphenated" on-line practice
of LC–MS. What has changed, though, is this: as an analytical method, LC–MS has become so ubiquitous in industry and research
that more practitioners now approach it as a single, integrated analytical process. Based upon the rapid growth of the American
Society of Mass Spectrometry (ASMS) indicated by the annual conference attendance in recent years, the cross-section of who
constitutes today's practitioners has broadened as well. We have abandoned the sense of technological duality that the hyphenated
usage implied. My 1997 article attempted to outline evolution of the mass spectrometer as it was becoming a true mass detector
"mixing significant technological events with significant commercialization initiatives over [those] 10 years." It fleetingly
acknowledged important events in the development of LC–MS to that point, such as Blakely and Vestal's 1983 publication on
thermospray which, though no longer used, was the first LC–MS enabling technology.1
John Fenn (along with Koichi Tanaka and Kurt Wüthrich) received the Nobel Prize in Chemistry, in 2002, for his work on the
most significant aspect of LC–MS practice — electrospray ionization (ESI) — based upon work published in the early 1980s.2,3 Among those receiving credit for commercializing the concept were Bruins and Covey who, along with Henion, published commercially
promising ESI designs in 1987.4A harbinger of things to come, the first truly hyphenated system appeared in 1982. Hewlett Packard's mass spectrometry detector
(MSD) used a gas chromatograph to introduce analytes into the mass spectrometer's ion source. Of course, the gas chromatograph
limited the MSD to analysing only compounds of sufficient vapour pressure. However, no such restriction attended coupling
a high performance liquid chromatography (HPLC) system to the mass spectrometer. LC–MS had its own problems: vacuum system
and flow-rate requirements evolved large, costly, often unreliable instruments.
In 1993, Waters (Milford, Massachusetts, USA) introduced a benchtop instrument for LC–MS. Designed to operate using particle
beam technology, which in the era of ESI exhibited certain performance issues, it nonetheless deserves footnote-level respect
for giving us true electron ionization (EI) spectra for an LC separation. That said, the first LC–MS designed for widespread
adoption is probably Vestec's thermospray-equipped, modified HP MSD, which the company offered at the 1986 Pittsburgh Conference
and Exposition (Pittcon) for the almost magical price of $100000. Thermospray of course faded quickly and so did the dream
of vastly capable but inexpensive LC–MS.
As is so often the case, the optimism of commercial interests proved unwarranted. In 1988, a year after Extrel Corporation
had introduced particle beam technology at Pittcon; Hewlett Packard (now Agilent Technologies, Santa Clara, California, USA)
introduced a version derived from the original particle beam instrument. The HP product manager claimed the interfacing of
LC and MS brought to the LC–MS market the reproducibility of results and ease-of-use characteristic of gas chromatography
(GC)–MS. In those days, industry watchers estimated market sales to be $15 to $20 million, with thermospray instruments accounting
for 60–80% of the business.5 Always a point of industry contention and one whose public discussion is typically avoided for reasons of competition, Finnigan
(now Thermo Fisher Scientific, Waltham, Massachusetts, USA) management succinctly stated at Pittcon 1993 that estimates of
market size were almost "guaranteed" to be incorrect and were "probably rather conservative". Indeed, the total market for
1993 was predicted at $640 million. In the years immediately following, it became obvious that both sides of the argument
were incorrect.
The early 1990s fell far short of sales expectations, the consequence of a general economic slowdown. (Remember, these were
the days when costly analytical purchases were driven largely by a rapidly building pharmaceutical industry.) A 1996 American
Chemical Society report cited 1991 sales exceeding $450 million, but with the caveat that "growth in these areas is difficult
to predict."