A Review on GC-MS Hyphenated Technique

 

Pankaj Thakur*, Upasana Thakur, Pooja Kaushal, Amar Deep Ankalgi,

Pramod Kumar, Aman Kapoor, Mahendra Singh Ashawat

Department of Pharmaceutical Analysis and Quality Assurance, Laureate Institute of Pharmacy,

Kathog, Jawalaji.

*Corresponding Author E-mail: thakurpankajsingh41@gmail.com

 

ABSTRACT:

The hyphenated technique is developed from the coupling of a separation technique and an on-line spectroscopic detection technology, GCMS, LC-MS, LC-FTIR, LC-NMR, and CE-MS. Gas chromatography combined with mass spectrometry is an important technique for identification and quantification of analytes in multifactor systems. GC-MS is highly effective and versatile analytical techniques with numerous scientific applications to cater the field of applied Sciences and Technology. This review elaborates the significant uses of this technique. It includes a brief discussion of the instrumental set-up and theory for the comprehensive GC × GC hyphenated with different detection techniques. It is fast and sensitive, provides a high peak capacity, and allows determination of thermally stable and volatile compounds.

 

KEYWORDS: Hyphenated Technique, GC-MS, Instrumentation and Application.

 

 


INTRODUCTION:

A hyphenated technique is combination of different-different analytical techniques.1 Chromatographic techniques are combined with mass spectroscopic techniques pure fractions of chemical components in the form of mixture was separated and spectroscopy produces important information for identification using standards.2 “The combination of this separation technique an on-line spectroscopic detection technology called as hyphenated technique.3 The term hyphenated techniques are the combination of separation-separation, separation-identificationand identification- identification techniques.

 

The term "hyphenation" introduced by Hirsch Feld which refer to the on-line combination of a separation technique and one or more spectroscopic detection techniques.4Now days this technique developed from a marriage of a separation technique and a spectroscopic detection technique, known as hyphenated technique.5 In 1980 Hirsh Feld was adopted the term “hyphenation” to describe a possible combination of two or more different instrumental analytical methods in a single run. The aim of the coupling is to obtain an information-rich detection for both identification and quantification compared to that with a single analytical technique.6-7

 

Types of hyphenated techniques:

GC-MS

GC-IR

GC-FTIR

LC-MS

LC-NMR

LC-IR

CE-MS

HPLC-DAD8-9HPLC-DAD8-9


 

Fig.1: Hyphenated techniques

 


GAS CHROMATOGRAPHY:

Gas chromatography (GC) is a common type of chromatography technique which is used in analytical chemistry for analyzing and separating compounds that can be vaporized without decomposition. GC used for testing the purity of compounds, separating the different components of a mixture. In preparative chromatography, GC used in prepares pure compounds from a mixture. In gas chromatography, a carrier gases are important and used as a mobile phase, mostly inert gases such as helium or an unreactive gas such as nitrogen are used. Helium is the most commonly used carrier gas. In an inert solid support which contain a microscopic layer of liquid/polymer inside a piece of glass or metal tubing called a column. The instrument used to perform gas chromatography is called a gas chromatograph (Figure 2)10-13

 

Fig. 2: Gas chromatography

 

Inert carrier gas helium is supplied from gas cylinders to the GCmanual or electronic (pneumatic) pressure controller regulates the pressure .The regulated carrier gas is supplied to the inlet and subsequently flows through the column and into the detector. The sample is injected into the heated injection port and it is volatilized and carried into the column by the carrier gas. The sample is separated in the column. The sample separates by differential partition of the analytes between the mobile and stationary phases. The sample eluted from the column, the carrier gas and analytes pass into a detector, which responds to some physicochemical properties of the analyte and an electronic signal was generate to measuring the amount of analyte present into the sample.Then the data system produces an integrated chromatogram. The temperature of the GC oven form in the ranges of 5 °C to 400 °C but can go as low as -25 °C with cryogenic cooling. Mass spectrometry is a powerful analytical technique that used to quantify known materials, to elucidate the structure and chemical properties of different molecules and identify unknown compounds within a sample. The complete process formed the conversion of the sample into gaseous ions, with or without fragmentation, which are then characterized by their mass to charge ratios (m/z) and relative abundances.14-17

 

Basic Principle:

A mass spectrometer occurs multiple ions from the sample under investigation; it then separates the ions according to their specific mass-to-charge ratio (m/z), and then records the relative abundance of each ion type.The first step in the mass spectrometric analysis of compounds is the production of gas phase ions of the compound, basically by electron ionization. This molecular ion undergoes fragmentation. Each ion of primary product derived from the molecular ion, undergoes fragmentation, and so on. The mass spectrometers separate the ions according to their mass-to-charge ratio, and are detected in proportion to their abundance. A mass spectrum is produced the molecules. It displays the result in the form of mass-to-charge ratio versusa plot of ion abundance. Ions provide information concerning the structure of their precursor molecule and the nature. In the spectrum of a pure compound, the molecular ion, if present, appears at the highest value of m/z (followed by ions containing heavier isotopes) and gives the molecular mass of the compound.The instrument consists of three major components:

 

Ion Source:

For producing gaseous ions from the substance being studied.

 

Analyzer:

For resolving the ions into their characteristics mass components according to their mass-to-charge ratio.

 

Detector System:

For detecting the ions and recording the relative abundance of each of the resolved ionic species.Furthermore, an example acquaintance framework is important with concede the examples to be concentrated to the particle source while keeping up the high vacuum prerequisites (~10-6 to 10-8 mm of mercury) of the strategy; and a PC is required to control the instrument, procure and control information, and contrast spectra with reference libraries.18-19

 

Fig. 3: Components of a Mass Spectrometer

 

GAS CHROMATOGRAPHY–MASS SPECTROMETRY (GC-MS):

Gas chromatography–mass spectrometry (GC-MS) is ahyphenated technique that joins the highlights of gas-chromatography and mass spectrometry to distinguish various substances inside a test. Uses of GC-MS incorporate medication location, fire examination, ecological examination, explosives examination, and ID of obscure examples, including that of material examples acquired from planet Mars during test missions as ahead of schedule as the 1970s.

 

GC-MS can likewise be utilized in air terminal security to recognize substances in gear or on people. it can distinguish follow components in materials that were recently thought to have crumbled past recognizable proof. Like fluid chromatography–mass spectrometry, it permits investigation and discovery even of minor measures of a substance’ GC-MS has been viewed as a "highest quality level" for measurable substance recognizable proof since it is utilized to play out a 100% explicit test, which emphatically distinguishes the nearness of a specific substance.A vague test only shows that any of a few out of a class of substances is available. The first on-line coupling of gas chromatography to a mass spectrometer was accounted for in 1959.The advancement of moderate and scaled down PCs helped in the disentanglement of the utilization of this instrument, just as permitted extraordinary upgrades in the measure of time to investigate an example.20-21

 

INSTRUMENTATION:

The GC-MS is made out of two significant structures obstructs: the gas chromatograph and the mass spectrometer.The gas chromatograph uses a slender segment which relies upon the segment's measurements (length, distance across, film thickness) just as the stage properties (for example 5% phenyl polysiloxane).The distinction in the compound properties between various particles in a blend and their relative proclivity for the stationary period of the segment will advance detachment of the atoms as the example ventures to every part of the length of the section.The atoms are held by the segment and afterward elute from the segment at various occasions and this permits the mass spectrometer downstream to catch, ionize, quicken, redirect, and recognize the ionized particles independently.The mass spectrometer does this by breaking every atom into ionized pieces and identifying these fragments.It is beyond the zone of imagination to expect to make an exact ID of a specific particle by gas chromatography or mass spectrometry alone.The mass spectrometry process ordinarily requires an unadulterated example while gas chromatography utilizing a conventional identifier can't separate between different particles that happen to set aside a similar measure of effort to go through the section, which brings about at least two atoms that co-elute.Some of the time two distinct particles can likewise have a comparative example of ionized pieces in a mass spectrometer joining the two procedures diminishes the chance of blunder, as it is incredibly far-fetched that two distinct atoms will act similarly in both a chromatograph and a spectrometer.In this manner, when a recognizing mass range shows up at a trademark maintenance time in a GC-MS examination, it commonly builds conviction that the analyte of intrigue is in the sample.nts utilizing their mass-to-charge proportion.22-24

 

Most common stationary phase:

1.     Separation of mixture of polar compounds : carbowax 20M (Polyethylene Glycol)

2.     Separation of mixture of non - polar compounds : OV101 or SE-30(Polymer of methysilicone)

3.     Methylester of fatty acids :DEGS (diethylene Glycol succitate)

4.     HP-5 (5% phenyl 95% dimethylpolysiloxane) fused silica (Agilent 19091S-433)25

 

Instruments components:

Carrier gas:

The Carrier gas must be chemically inert, commonly used gases include nitrogen, argon, and carbon dioxide. The carrier gas was helium at a constant flow rate of 3 𝑚𝐿𝑚𝑖𝑛.

 

Sample injection port:

The most the most widely recognized strategy is where a microsyringe is utilized to infuse the example through an elastic septum into a glimmer vaporizer pot at the leader of the segment.The temperature of the example port is as a rule around 50 °C higher than the breaking point of the least unstable compound of the example.

 

For packed column, test size range from 0.1 microlitres up to 20 microlitres.

 

Capillary column, sample range around 10-3 microlitre.

 

For capillary GC-MS slip/slitless injection is used.

 

The infusion can be utilized in one of the two modes, slipt or slitless. The injector containing radiator chamber containing a glass line into which the example is infused through the septum.The carrier gas enters the chamber and can leave by the three roots.

 

Column:

There are mainlytwo type of columnPacked and Capillary.

 

Packed columns:

Packed columnscontain a finely inert, solid support material coated with liquid stationary phase. Most packet column is 1.5-10m in length and an internal diameter is 2-4mm.

 

Capillary column:

Capillary column have an internal diameter of a 0.1 mm. They can be two types; wall-coated open tubular (WCOT) or support-coated open tubular (SCOT). Wall-coated columns consist of a capillary tube whose walls are coated with liquid stationary phase. In support-coated columns, the inner wall of the capillary is lined with a thin layer of support material such as diatomaceous earth, onto which the stationary phase has been adsorbed. SCOT columns are generally less efficient than WCOT columns. Both types of capillary column are more efficient than packed columns.26-27

 

Mass instrumentation:

After the particles venture to every part of the length of the section, go through the exchange line and go into the mass spectrometer they are ionized by different techniques with commonly just a single strategy being utilized at some random time.When the example is divided it will at that point be identified, for the most part by an electron multiplier, which basically transforms the ionized mass section into an electrical sign that is then distinguished.The ionization technique chosen is independent of using full scan or SIM.

 

Electron ionization:

By a long shot the most widely recognized and maybe standard type of ionization is electron ionization (EI). The atoms go into the MS (the source is a quadrupole or the particle trap itself in a particle trap MS) where they are shelled with free electrons discharged from a fiber, much the same as the fiber one would discover in a standard light. The electrons besiege the atoms, making the particle piece in a trademark and reproducible manner. This "hard ionization" system brings about the making of more parts of low mass-to-charge proportion (m/z) and barely any, atoms moving toward the sub-atomic mass unit.Hard ionization is considered by mass spectrometrists as the utilize of sub-atomic electron siege, though "delicate ionization" is accuse by sub-atomic crash of a presented gas.The atomic discontinuity design is needy upon the electron vitality applied to the framework, normally 70 eV (electron Volts).The utilization of 70 eV encourages examination of created spectra with library spectra utilizing maker provided programming or programming created by the National Institute of Standards (NIST-USA).Otherworldly library look through utilize coordinating calculations, for example, Probability Based Matching and speck productcoordinating that are utilized with strategies for investigation composed by numerous technique institutionalization organizations.Wellsprings of libraries incorporate NIST, Wiley, the AAFSand instrument producers.28-31

 

Cold electron ionization:

The "hard ionization" procedure of electron ionization can be mollified by the cooling of the atoms before their ionization, bringing about mass spectra that are more extravagant in data. Right now chilly electron ionization (cold-EI) the atoms leave the GC section, blended in with included helium make up gas and venture into vacuum through an uncommonly planned supersonic spout, framing a supersonic sub-atomic bar (SMB). Crashes with the make-up gas at the growing supersonic fly decrease the inward vibrational (and rotational) vitality of the analyte atoms, henceforth lessening the level of discontinuity brought by the electrons during the ionization procedure. Cold-EI mass spectra are described by a rich atomic particle while the standard discontinuity design is held, in this way making cold-EI mass spectra good with library search ID methods. The upgraded sub-atomic particles increment the distinguishing proof probabilities of both known and obscure mixes, intensify isomer mass ghostly impacts and empower the utilization of isotope plenitude examination for the clarification of basic formulae.32-36

 

Time-of-Flight (TOF) MS:

In contrast to attractive division and quadrupole MS, Time-of-Flight (TOF) MS is a beat and non-examining MS. It has a basic development, comprising of a quickening agent, a sans field district, a reflectron and finder inside a high vacuum chamber called a flight tube (Figure 4). TOF MS isolates and identifies particles of various m/z by estimating the time taken for the particles to go through a sans field locale. These ions are accelerated by applying a high acceleration voltage between the electrodes. Given a steady quickening voltage just as active vitality, every particle flies at its one of a kind speed inside the flight cylinder to arrive at the particle finder, which is higher for particles with littler masses and lower for particles with bigger masses.37-41

 

Fig. 4 Time-of-Flight (TOF)

 

Detectors:

The most widely recognized sort of mass spectrometer (MS) related with a gas chromatograph (GC) is the quadrupole mass spectrometer, in some cases alluded to by the Hewlett-Packard (presently Agilent) exchange name "Mass Selective Detector" (MSD). Another moderately normal indicator is the particle trap mass spectrometer.Furthermore one may locate an attractive division mass spectrometer; anyway these specific instruments are costly and cumbersome and not normally found in high-throughput administration research centers.Different indicators might be experienced, for example, time of flight (TOF), pair quadrupoles (MS-MS) (see beneath), or on account of a particle trap MSn where n shows the number mass spectrometry stages.42-46

 

APPLICATIONS:

Environmental monitoring and clean-up:

GC-MS is turning into the device of decision for following natural contaminations in the earth.The expense of GC-MS hardware has diminished altogether, and the dependability has expanded simultaneously, which has added to its expanded appropriation in ecological investigations.47-51

 

Criminal forensics:

GC-MS can examine the particles from a human body so as to help connect a criminal to a wrongdoing.The examination of fire flotsam and jetsam utilizing GC-MS is settled, and there is even a set up American Society for Testing and Matrials (ASTM) standard for fire trash investigation.GCMS/MS is particularly valuable here as tests regularly contain complex lattices and results, utilized in court, should be exceptionally precise.52-57

 

Law enforcement:

GC-MS is progressively utilized for location of unlawful opiates, and may inevitably supersede sedate sniffing hounds..A basic and particular GC-MS technique for distinguishing maryjane use was as of late created by the Robert Koch-Institute in Germany.It includes recognizing a corrosive metabolite of tetrahyhydrocannabinol (THC), the dynamic fixing in pot, in pee tests by utilizing derivatization in the example readiness.GC-MS is likewise ordinarily utilized in legal toxicology to discover drugs and additionally harms in organic examples of suspects, unfortunate casualties, or the expired. In medicate screening, GC-MS techniques every now and again use fluid extraction as a piece of test arrangement, in which target mixes are removed from blood plasma.58-60

 

Sports anti-doping analysis:

GC-MS is the fundamental apparatus utilized in sports hostile to doping research centers to test competitors' pee tests for disallowed execution improving medications, for instance anabolic steroids.61-63

 

Security:

Post–September 11 advancement, dangerous discovery frameworks has become a piece of all US air terminals.These frameworks run on a large group of innovations, huge numbers of them dependent on GC-MS. There are just three makers affirmed by the FAA to give these systems, one of which is Thermo Detection (in the past Thermedics), which delivers the EGIS, a GC-MS-based line of explosives finders.The other two makers are Barringer Technologies, presently possessed by Smith’s Detection Systems, and Ion Track Instruments, some portion of General Electric Infrastructure Security Systems.64-65

 

Chemical warfare agent detection:

As a feature of the post-September 11 drive towards expanded capacity in country security and general wellbeing readiness, conventional GC-MS units with transmission quadrupole mass spectrometers, just as those with round and hollow particle trap (CIT-MS) and toroidal particle trap (T-ITMS) mass spectrometers have been changed for field convenientce and approach constant discovery of synthetic fighting operators (CWA, for example, sarin, soman, and VX.23 These unpredictable and enormous GC-MS frameworks have been altered and designed with resistively warmed low warm mass (LTM) gas chromatographs that decrease investigation time to fewer than 10% of the time required in conventional research facility frameworks.24 Furthermore, the frameworks are littler, and progressively portable, including units that are mounted in versatile expository research facilities (MAL, for example, those utilized by the United States Marine Corps Chemical and Biological Incident Response Force MAL and other comparative labs, and frameworks that are hand-conveyed by two-man groups or people, much ado to the littler mass identifiers.Contingent upon the framework, the analytes can be presented by means of fluid infusion, desorbed from sorbent tubes through a warm desorption process, or with solid phase micro extraction (SPME).66-68

 

Chemical engineering:

Dependent upon the system, the analytes can be displayed by methods for liquid imbuement, desorbed from sorbent tubes through a warm desorption process, or with solid stage little scope extraction (SPME).GC-MS is additionally used in the recognizable proof of nonstop stage segment in a savvy material, Magnetorheological (MR) liquid.69

 

Food, beverage and perfume analysis:

Nourishments and refreshments contain various sweet-smelling intensifies, some normally present in the crude materials and some framing during handling.GC-MS is broadly utilized for the examination of these mixes which incorporate esters, unsaturated fats, alcohols, aldehydes, terpenes and so on.It is likewise used to distinguish and gauge contaminants from decay or debasement which might be hurtful and which are frequently constrained by legislative offices, for instance pesticides.70

 

Astrochemistry:

A few GC-MS have left earth. Two were brought to Mars by the Viking program.Venera 11 and 12 and Pioneer Venus examined the air of Venus with GC-MS.29 The Huygens probe of the Cassini–Huygens mission landed one GC-MS on Saturn's largest moon, Titan. The MSL Curiosity rover's Sample Analysis at Mars (SAM) instrument contains both a gas chromatograph and quadrupol mass spectrometer that can be used in tandem as a GC-MS. The material in the comet 67P/Churyumov–Gerasimenko was analysed by the Rosetta mission with a chiral GC-MS in 2014.71

 

Medicine:

Many innate metabolic infections otherwise called intrinsic blunders of digestion (IEM) are presently perceptible by infant screening tests, particularly the testing utilizing gas chromatography–mass spectrometry.GC-MS can decide mixes in pee even in minor focus.These mixes are ordinarily not present however show up in people enduring with metabolic disarranges.This is progressively turning into a typical method to analyze IEM for prior finding and foundation of treatment in the long run prompting a superior result.In mix with isotopic naming of metabolic aggravates, the GC-MS is utilized for deciding metabolic action. Most applications are based on the use of 13C as the labelling and the measurement of 13C-12C ratios with an isotope ratio mass spectrometer (IRMS); an MS with a detector designed to measure a few select ions and return values as ratios.72-73

 

CONCLUSION:

The GC-MS is powerful hyphenated techniques for the analysis of compound with their relative mass. It has broad range of applications that helps to academic research, quality control aswell as industrial applications. It is automated system gives fast, reproducible and effective results that is a key important role in advancement of Science and Technology. GC-MS is widely used in pharmaceutical industries for analytical research and development, quality control, quality assurance, production for active pharmaceutical ingredients, bulk drugs and formulations. This versatile analytical technique could be explored for better prospects in future.

 

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Received on 12.04.2021       Modified on 18.05.2021

Accepted on 21.07.2021   ©Asian Pharma Press All Right Reserved

Asian J. Pharm. Ana. 2021; 11(4):285-292.

DOI: 10.52711/2231-5675.2021.00049