Michael P. Balogh

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" online 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 (4).

In 1993, Waters (Milford, Massachusetts) 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 $100,000. 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) 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 typically is avoided for reasons of competition, Finnigan (now Thermo Fisher Scientific, Waltham, Massachusetts) 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."