S E C T I O N 1

THE FUNDAMENTALS OF GC/MS

C H A P T E R 1

c0010 INTRODUCT ION AND HISTORY

p0010 Gas chromatography/mass spectrometry (GC/MS) is the most ubiquitousanalytical technique for the identification and quantitation of organic sub-stances in complex matrices. The GC-MS is indispensable in the fields ofenvironmental science, forensics, health care, medical and biologicalresearch, health and safety, the flavor and fragrances industry, food safety,packaging, and many others. The instrumentation ranges in price fromnearly 1 million dollars to just a few thousand. The size is large enough torequire a 4-m� 4-m room to that of an average briefcase (Figure 1.1).

p0020 GC/MS is the synergistic combination of two powerful microanalyticaltechniques. The gas chromatograph separates the components of a mixture intime, and the mass spectrometer provides information that aids in the structuralidentification of each component. This combination has several advantages [1].First, it separates components of a complex mixture so that mass spectra ofindividual compounds can be obtained for qualitative purposes; second, it canprovide quantitative information on these same compounds. Mass spectro-metry ionization techniques that require gas-phase analytes are ideally suited toGC/MS because sample volatility is a requirement of gas chromatography(GC). The gas chromatograph, the mass spectrometer, and the interfacelinking these two instruments are described in the following chapters.

p0030 GC/MS can provide a complete mass spectrum from a few femtomolesof an analyte; ideally, this spectrum gives direct evidence for the nominalmass and provides a characteristic fragmentation pattern or “chemical”fingerprint that can be used as the basis for identification along with thegas chromatograph retention time.

p0040 Mass spectrometry had its origin ca. late 1800s with the work of JohnJoseph Thomson [2] and Wilhelm (Willy) Carl Werner Otto Fritz FranzWien [3]. Mass spectrometry was dominated by the measurement of the var-ious nuclides* that made up the known elements of the time until the mid-partof the 20th century when the mass spectrometer’s use for the analysis ofpetroleum products and other organic compounds began to gain momentum.

* A nuclide is an atomic species characterized by the total number of neutrons and protons inthe nucleus. Although not synonymous with isotope, for the purposes of this book, anuclide is one of the many atomic species that are characterized by both their atomicnumber and their mass number.

Gas Chromatography and Mass Spectrometry � 2010 by Academic Press. Inc.DOI: 10.1016/B978-0-12-373628-4.00001-0 All rights reserved.

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p0050 Chromatography began about the same time as mass spectrometry(ca. 1900) with the seminal publication by Mikhail Semenovich Tsvet(two other papers appeared in German that are often mistakenly referencedas the beginning of chromatography: Tswett MS) [4–7]. The early practiceof chromatography consisted of the application of liquid samples to shorthomemade columns of various absorbents or to absorbent paper. The reportof partition chromatography by Archer John Porter Martin and RichardLaurence Millington Synge [8, 9] in 1941 led to the development of GC byMartin and Anthony Tarfford James [10, 11] in 1950.

p0060 Very soon after the development of GC, attempts to interface the gaschromatograph with the mass spectrometer began. This was a naturaldevelopment as the gas chromatograph separates organic compounds, andthey eluted from the column in a purified state in the gas phase; and themass spectrometers of that time required pure gas-phase analytes for ioniza-tion. However, the original gas chromatographs used packed columns withflow rates (20–30 mLmin�1) that overwhelmed the required low pressuresof the mass spectrometer. One of the main obstacles to the technique ofGC/MS was this incompatibility in pressure requirements. Today’s instru-mentation is faced with far fewer such problems because of the use ofcapillary columns with flow rates that are usually 1.5 mLmin�1 or less,and much better pumping systems to maintain the vacuum required for themass spectrometer.

p0070 As will be forever debated, the actual first attempt to interface the gaschromatograph and the mass spectrometer was accomplished by eitherJoseph C. Holmes and Francis A. Morrell at Philip Morris, Inc., in Rich-mond, Virginia, who published their work on the interfacing of a gaschromatograph with a Consolidated Engineering Corporation (CEC)Model 21–103B magnetic sector mass spectrometer in 1957 [12] or Roland

f0010 Figure 1.1 The Thermo Scientific DFS GC/MS system (left), a high-resolutiondouble-focusing magnetic-sector GC-MS that plays a significant role in the HR SIM

4 Chapter 1

S. Gohlke and Fred McLafferty (both at Dow Chemical Company inMidland, Michigan, at that time) who presented their work on interfacinga gas chromatograph with a time-of-flight (TOF) mass spectrometer at the129th National American Chemical Society (ACS) meeting in April of 1956in a symposium on Vapor Phase Chromatography [13]. This work was firstpublished in a paper authored only by Gohlke in the April 1959 issue ofAnalytical Chemistry, almost a year after it was received by the journal onMay 31, 1958 [14], and almost 3 years after the 129th ACS meeting. TheHolmes/Morrell work was first presented at the Fourth Annual Meeting ofAmerican Society for Testing and Materials (ASTM) Committee E-14 onMass Spectrometry and Allied Topics in Cincinnati, Ohio, in May of 1956.

p0080 The GC-MS of today is a unique instrument. Gohlke/McLafferty andHolmes/Morrell treated their systems as a gas chromatograph being used asan inlet to a mass spectrometer; there are some who would treat the massspectrometer as a detector for the gas chromatograph. Neither of these istrue. The mass spectrometer is not a gas chromatograph detector, andthe gas chromatograph is not an inlet for the mass spectrometer. It isimportant to remember that GC/MS is as different from either GC ormass spectrometry as GC and mass spectrometry are from one another.This is because an elevated pressure is required to separate the componentsof a mixture in a gas chromatograph and a greatly reduced pressure isrequired to separate the ions of various mass-to-charge ratios (m/z values)that characterize a pure component of that mixture.

p0090 Both the Gohlke/McLafferty and the Holmes/Morrell attempts atinterfacing the gas chromatograph and the mass spectrometer involvedsplitting a small portion of the gas chromatograph eluate to the massspectrometer, with the remainder being diverted to either a conventionalgas chromatograph detector or the atmosphere. This was necessary tocircumvent the conflicting high/low-pressure needs of the two instru-ments. In the 1960s, devices were developed to enrich the eluatefrom packed gas chromatograph columns with respect to the analyte.These devices, for the most part, have now fallen into disuse because ofthe use of capillary gas chromatograph columns that produce eluates muchricher in analyte concentration than packed columns and improvedvacuum systems. Today’s modern instrument has the exit end of the gaschromatograph column placed directly in the ion source of the massspectrometer.

p0100 A very significant factor in the evolution of GC/MS was the develop-ment of data systems. When GC/MS was first being explored, it was readilyseen that the potential for the volume of data was overwhelming. A10-minute chromatographic run, acquiring spectra at the rate of one persecond, would result in a total of 600 spectra. Extracting the spectraassociated with various chromatographic peaks and then dealing with thepresence of mass spectral peaks that were due to background associated with

Introduction and History 5

the sample or the gas chromatograph column was quite daunting.* It was notuntil the development and commercialization of the minicomputer (ca. 1965)that it was possible to bring the computer to the GC-MS. Before that time, thedata had to be brought from the mass spectrometer to the computer and inputmanually. When Digital Equipment Corp. (acquired by Compaq Computer,whichwas then acquired byHewlett–Packard) introduced the first commercialminicomputer, the PDP-8, one of its first uses was to acquire and process GC/MS data [15, 16]. Users quickly warmed to the abilities and speeds of thesecomputers. As the minicomputer evolved, the speeds began to fade because ofthe overhead of the operating systems and software used to develop the GC/MS applications. As the speed of the second-generation individual computer(the microcomputer) continued to increase, the speed of the early 1970s GC/MS data systems was once again realized near the end of the 1990s.

p0110 Improvements in capillary column injectors [17–20], development of fusedsilica capillary columns [21], development of electronic flow and pressurecontrol [22], and improvements in the bleed characteristics of open-tubularwall-coated columns [22] have led to easier-to-useGC/MS systemswith lowerand lower limits of detection. Improvements in gas chromatograph columnstability, controlled rapid heating rates for fast chromatography, and reducedoven cool-down times have also partially contributed to the technique.

p0120 The GC/MS instrument of today allows for more flexibility in ioniza-tion, speed of data acquisition, and ease of use for less-skilled practitionerswho are more interested in answers than the art and science of the techni-que, and, very importantly, much smaller size. The GC/MS floor-standinginstrumentation of the 1970s and early 1980s would fill a 10-m� 10-mroom. Some of today’s laboratory instrumentation can be accommodatedby 2–4 square feet of benchtop space.

p0130 GC/MS is limited to analytes that are not only volatile and thermallylabile but can also withstand the harsh partitioning conditions of the gaschromatograph.** Even with this limitation, there are many analytes thatcan only be separated from complex mixtures and identified by GC/MS.Compounds that exist only in the gas phase at temperatures below 100°Ccannot be separated and ionized using techniques other than GC/MS. Dueto the ability to form stable, volatile derivatives of many compounds not

* The term “peak” has already been used twice in this paragraph: once referring to thechromatographic peak and once referring to the mass spectral peak. This is an excellentexample why it is always important to qualify the type of peak being discussed when GC/MS is involved. In GC/MS, the word “peak” should never be used unless it is preceded by“chromatographic” or “mass spectral”.

** Compounds that can be ionized by atmospheric pressure chemical ionization (APCI) usedin combination with LC/MS must be volatile and nonlabile-like compounds analyzed byusing GC/MS; however, in LC/MS, the analytes do not have to withstand the rigors ofthe gas chromatographic partitioning process. Therefore, the range of analytes for APCILC/MS can be expanded in the direction of lack of volatility and thermal lability.

6 Chapter 1

suited for GC/MS in their natural forms, the number of possible analytescan be significantly expanded. Because of the extensive fragmentationexperienced during electron ionization (EI), it is the most widely usedGC/MS ionization technique; there are many compounds that produceunique patterns that can be used in conjunction with gas chromatographicretention-time data for an unambiguous identification.

p0140 Limits of detection can be lowered using special data acquisition techniquessuch as selected ion monitoring (SIM).* Three-ion ratios can be used forunambiguous identification because of extensive fragmentation when SIM isemployed** [23]. Formation of electrophilic derivatives through the use ofreagents such as perfluoropropionic anhydride allows limits of detection to begreatly reduced in the presence of complex matrices due to the ability to takeadvantage of techniques such as electron capture/resonance ionization.

p0150 Figure 1.2 is a conceptual illustration of the GC-MS. There are anumber of variables associated with a GC/MS analysis. These variables fall

CIReagent

gas

Ionsource

Detectorm/z AnalyzerIons Ions

Vacuum

Computer/datasystem

GC/MSinterface

Gaschromatograph

Inlets (injectors, gassampling valves, probe)

GCcolumn

GC carrier gasmobile phase

Direct inletDirect insert

(DCI)Probes

f0020 Figure 1.2 Conceptual illustration of the GC/MS system reveals the majorcomponents: the GC and its inlets, other detectors, the ion source, inlets other thanthe GC to the mass spectrometer, the m/z analyzer, the ion detector, and the datasystem. The components of the mass spectrometer must be maintained under vacuum,allowing ions to be independent of all other matter.

* In many cases, spectral acquisition of GC/MS data involves a contiguous range of m/z valuesrecording any ion abundances at any m/z value in the range. Instruments such as thetransmission quadrupole mass spectrometer can be operated where each acquisition cycleof the instrument measures the ion current for a few (usually less than 8) m/z values byjumping from value to value and spending a specified “dwell time” on each ion to measure itsion current (abundance). This technique is called selected ion monitoring (SIM).

** Three-ion ratios can also be used with full-spectrum acquisition methods. Although it maynot appear to be necessary to use these ratios when a complete spectrum is generated by full-spectrum acquisition, the three-ion ratio is required in some regulated methods, such asscreening for drugs of abuse.

Introduction and History 7

broadly into two categories—instrumental variables and operational vari-ables. For the most part, the instrumental variable must be decided beforethe actual GC-MS is acquired. The operational variables are those decidedfor each specific analysis.

s0010 1.1 . I N S T RUMEN T A L VAR I A B L E S

p0160

o0010 •p0170 Automation (requiring some type of autosampler).o0020 •p0180 Type of sample introduction(s)—e.g., type of gas chromatograph injector,

direct introduction, pyrolysis, gas sampling valves, etc. If subambientcooling is required, will it be CO2 or LN2?

o0030 •p0190 Gas chromatograph oven-temperature requirements—e.g., subambientcooling (CO2 or LN2 option), rapid temperature ramping, minimalcool-down times, etc.

o0040 •p0200 Requirement (if any) for conventional gas chromatograph detection.o0050 •p0210 Gas chromatographic mobile phase to be used.o0060 •p0220 Type of mass spectral ionization—e.g., EI, chemical ionization (CI), field

ionization (FI), electron capture/negative ionization (ECNI), etc.o0070 •p0230 Type of m/z analyzer—this is based on data requirements such as mass

accuracy, spectral acquisition rate, lower limits of detection, linearity forquantitation, etc.

o0080 •p0240 Data system requirements—e.g., analysis reporting, database searching,automated quantitation, accurate mass from integer data, etc.

p0250 Some of these instrument variables can be added after the purchase andinstallation of the initial instrument, like software items; others such as analyzerand ionization types are not changeable. The same could be true for the sampleintroduction types and oven-temperature requirements. This is why a careful“needs analysis” should be performed before the instrument is purchased.

s0020 1.2 . OP E R A T I O N A L VAR I A B L E S

p0260

o0090 •p0270 Gas chromatograph column to be used—e.g., length, diameter, stationaryphase, thickness of stationary phase, etc.

o0100 •p0280 Injector settings—e.g., temperature, split ratios, split times, etc.o0110 •p0290 Need for flow-rate adjustment to obtain proper linear velocity of mobile

phase.o0120 •p0300 Calibration of m/z scale.o0130 •p0310 Gas chromatograph oven-temperature program rate(s)—e.g., initial hold

time and temperature, temperature ramp(s), upper temperature and holdtime, cool-down time, etc.

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o0140 •p0320 Temperature of interface between gas chromatograph and massspectrometer.

o0150 •p0330 Temperature of ion source and analyzer.o0160 •p0340 Type of ionization—e.g., EI, CI, FI (may require hardware change and

introduction of an auxiliary gas).o0170 •p0350 m/z range to be acquired.o0180 •p0360 Rate of spectral acquisition (may involve stating number of spectra to be

averaged before storing data).o0190 •p0370 Spectral acquisition type (centroid (default) or profile) based on

instrument type.

Componentdetection andquantitation

Ion statisticsSample utilizationefficiency and ion

compaction

No. of resolvedelementsm/z range

×resolution

MS

info

rmat

ion LC

information

Spectralgeneration

rate

Spectralinterpretation

Chromatographicresolution

f0030 Figure 1.3 Conceptual illustration of the dilemma created by scan speed versuschromatographic peak width. Too slow of a spectral acquisition rate results in loss ofchromatographic fidelity. Too fast of a scan speed results in poor spectral quality.

Introduction and History 9

p0380 The various gas chromatograph sample inlets, sample introduction methods,columns, GC detectors, and operating conditions are described in Chapter 2.The reason the gas chromatograph mobile phase, column size, and ioniza-tion type need to be known at the time of an instrument purchase is that thishas bearing on the pumping system required for the m/z analyzer. This willbe explained in more detail in Chapter 4.

p0390 GC involves a lot more than just selecting an appropriate column length,diameter, and stationary phase. With modern open-tubular columns, sam-ple injection has become as significant as the column selection. As detailedin Chapter 2, there are several different types of injectors, the most widelyused injector is the so-called split/splitless injector used for a spilt or asplitless injection. Analytes are usually present in a solvent. Selectionof the solvent, again, is as important as the column selection. Even thoughGC conditions are provided for many types of individual compounds inSection II, there are many analyses that require the determination of multi-ple types of compounds at the same time. For this reason and others, GC/MS is an experimental science. More often than not, an analysis must bedeveloped. The chromatographic and data acquisition must be determinedempirically.

p0400 The most widely used ionization technique in GC/MS is EI. Probablygreater than 90% of all GC/MS analyses are performed using EI. Manyinstruments require a physical change in the ion source when switchingfrom one ionization technique to another. The internal ionization quadru-pole ion trap (QIT) allows for EI and CI without any physical changes.Some manufacturers have combination EI/CI ion sources and others pro-vide instructions for obtaining EI data from CI sources. FI is the least usedGC/MS ionization technique and is only offered by two instrument man-ufacturers: Waters Corp. as a TOF and tandem quadrupole* instrument andJEOL as a TOF GC/MS system. Another ionization technique that wasavailable in the past for GC/MS is atmospheric pressure chemical ionization(APCI). There are no commercial instruments offering this technique at thistime. A paper was published with instructions on how to configure anatmospheric pressure ionization (API) instrument (mostly APCI and

*Tandem quadrupole is a term used to describe an instrument used for mass spectrometry/mass spectrometry (MS/MS). This instrument is sometimes referred to as a tandem-in-spaceinstrument, which means that ions from an initial ionization isolated by one mass spectro-meter are activated in such a way as to bring about their subsequent decomposition. Theseions produced by this decomposition of a precursor ion are then separated according theirm/z values, using a second m/z analyzer. The instrument is called a triple quadrupolebecause the two tandem QMF instruments are separated by a third device which bringsabout the collisional activation of the precursor ion. In the original design of this instru-ment, this third device was also a quadrupole operated in such a way as to be used only forcollisional activation and not ion separation. Today, this third device is usually not aquadrupole but the name triple quadrupole remains.

10 Chapter 1

electrospray ionization (ESI) instruments used in liquid chromatography(LC)/MS) to take the eluate from the gas chromatograph for APCI [24].

p0410 ECNI, also known as resonance electron capture/negative ionization, isanother somewhat widely used GC/MS technique because of the low detec-tion limits that can be obtained for electrophilic compounds such as halo-genated pesticides or halogenated derivatives. Due to the specificity of thistechnique, matrix compounds will not be detected for extremely low limitsof quantitation, especially when used in conjunction with an SIM analysis.

p0420 GC/MS has used many types of m/z analyzers to separate ions accordingto their m/z values. The device that is the most ubiquitous in GC/MSinstrumentation is the transmission quadrupole analyzer also known as thequadrupole mass filter (QMF). The device that follows this in popularity isthe QIT. Both of these devices are limited to producing data with an integerm/z value. Such data does not produce unambiguous elemental composi-tion for ions. However, an accurate mass measurement, within +0.1millimass units, does provide an unambiguous elemental composition.This has led to an increased popularity of the reflectron TOF analyzer,which will generate such data. The TOF provides lower detection limitsthan can be achieved with the QMF analyzer and does not produce skewedspectra due to spectral acquisitions occurring during rapid changes in theconcentration of the analyte in the ion source due to the chromatographicpeak width. The TOF analyzer will acquire spectra at a faster rate than canbe achieved with any other type of analyzer. Software has been developedthat allows for the assignment of accurate m/z values to QMF and QIT datathrough the use of mass spectral peaks of known purity and known exact m/z values, which has expanded the utility of these instruments.

p0430 Magnetic/electric-sector instruments (the double-focusing mass spectro-meter), along with magnetic-sector (single-focusing) instruments that domi-nated mass spectrometry until the commercialization of the QMF byFinnigan Corp. (now Thermo Scientific of Thermo Fisher), Hewlett–Packard (the analytical instrument division of HP is now part of AgilentTechnologies), and Extrel (now known as Extrel Mass Spectrometers(EMS)) in the late 1960s and early 1970s, are still in limited use andcommercially available from at least three different manufacturers.

p0440 GC/MS/MS (a.k.a. tandem mass spectrometry) is another techniquethat is being increasingly employed for various types of analyses and willbe discussed in more detail in Chapter 4. GC/MS/MS is commerciallylimited to the use of the triple quadrupole instrument (tandem-in-space)and to the QIT systems (tandem-in-time). Although commercially avail-able, the Fourier transform ion cyclotron resonance (FTICR) mass spectro-meter (the magnetic ion trap) has also been used for GC/MS. Theseinstruments are capable of very accurate mass measurements, but due totheir complex operation, need for a cryogenically cooled superconductingmagnet, and high initial cost, they are rarely found in a GC/MS laboratory.

Introduction and History 11

p0450 GC/MS presents a paradox. As GC has developed, the width of thechromatographic peak has continually been reduced, i.e., the elution timefor a component has become less. Acquisition of a mass spectrum from ascanning beam-type instrument (the QMF and the double-focusing sectorinstrument) is obtained over a finite period. Narrow chromatographic peaksresult in rapid changes of analyte concentration in the ion source during theacquisition of a single spectrum. This spectrum can exhibit a skew (relativeintensities of peaks at different m/z values that are different from whatwould be observed if there was no change in concentration in the ionsource during the spectral acquisition). This skew will not be that repro-ducible and will make searches against standard mass spectral databasesdifficult. Shorter acquisition time can reduce the spectral skewing; however,the quality of the spectrum can deteriorate because the time spent measur-ing the ion current for any single m/z is so short that there is such a poorsignal-to-noise ratio that the spectrum is uninterpretable. Reducing theperiod of elution for the analyte from the gas chromatograph columnwould greatly reduce the chromatographic resolution (the peak capacity).This reduced elution period would also have a tendency to increase theanalysis, and with the current interest in fast GC to shorten analysis times,this would not be acceptable. Instrument companies are offering QMF m/zanalyzers with shorter “scan time” by reducing the noise, but the minimalsignal will remain the same. This paradox, in part, is the reason that there isan increased interest in the pulsed instruments such as the QIT and TOF.

p0460 New practitioners enter the field of GC/MS, and, like all newcomers,they lack the experience needed to do many of the tricks that come withtime spent in developing methods and interpreting data. This book shouldmake that path to gaining the experience and knowledge easier and aid inresolving some of the various paradoxes that will be encountered.

REFERENCES

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3. Wien, W. (1898). Untersuchungen über die elektrische Entadung in verdünnten Gasen.Annalen der Physik und Chemie, 65, 440-52.

4. Tsvet, M. S. (Mswett—German Transcription of the name). (1903). A new category ofadsorption phenome and its application to biochemical analysis. Travl. Soc. NaturalistesVarisovic, 14 (Russian).

5. Tsvet, M. S. (Mswett—German Transcription of the name). (1972). Tswett centenaryissue. J. Chromatogr., 73(2), 303.

6. Tsvet, M. S. (Mswett—German Transcription of the name). (1906). Ber. Deut. Bot. Ges.,24, 316, 384.

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7. Tswett, M. S. (1910). Les Chromophless Dans Le Monde Végétal et Animal. Varsovie(French), Paris.

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10. James, A. T., Martin, A. J. P. (1951). Liquid-gas partition chromatography. Biochem.J. Proc., 48, VII.

11. James, A. T., Martin, A. J. P. (1952). Gas liquid partition chromatography: a techniquefor the analysis of volatile material. Analyst, 77, 915-32.

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13. Gohlke, R. S., McLafferty, F. W. (1993). Early GC-MS. J. Am. Soc. Mass Spectrom., 4,367-71.

14. Gohlke, R. (1959). Time-of flight mass spectrometry and gas liquid partition chroma-tography. Anal. Chem., 31, 535-41.

15. Reynolds, W. E., Bacon, V. A., Bridges, J. C., Coburn, T. C., Halpern, B., Lederberg,J., Levinthal, E. C., Steed, E., Tucker, R. B. (1970). A computer operated mass spectro-metry system. Anal. Chem., 42, 1122-9.

16. Sweeley, C. C., Ray, B. D., Wood, W. I., Holland, J. F. (1970). On-line digitalcomputer system for high-speed single focusing mass spectrometry. Anal. Chem., 42,1505-16.

17. Desty, D. H., Goldrup, A., Whyman, B. A. F. (1959). The potentialities of coatedcapillary columns for gas chromatography in the petroleum industry. J. Inst. Petro., 45,287-98.

18. Schomburg, G. (1981). Sampling systems in capillary chromatography. In: Proceedings ofthe Fourth International Symposium on Capillary Chromatography (R. E. Kaiser, ed.),pp. 371-404. Huethig, Heidelburg, Germany.

19. Zlatkis, A., Walker, J. Q. (1963). Direct sample introduction for large bore capillarycolumns in gas chromatography. J. Gas Chromatogr., 1(5), 9-11.

20. Grob, K., Grob, K., Jr. (1978). On-column injection onto glass capillary columns.J. Chromatogr. A., 151(21), 311-20.

21. Dandeneau, R. D., Zerenner, E. H. (1979). An investigation of glasses for capillarychromatography. J. High. Res. Chromatogr., 2(6), 351-6.

22. Bartle, K. D., Myers, P. (2002). History of gas chromatography. Trends Anal. Chem.,21(9.10), 547-57.

23. Sphon, J. A. (1978). Use of mass spectrometry for confirmation of animal drug residues.J. Assoc. Off. Anal. Chem., 81(5), 1247-52.

24. McEwen, C. N., McKay, R. G. (2005). A combination atmospheric pressure LC/MS-GC/MS ion source: advantages of dual AP-LC/MS:GC/MS instrumentation. J. Am. Soc.Mass Spectrom., 16(11), 1730-8.

Introduction and History 13