Analytical Review of Integrated Gas Chromatography (GC) Methods by FTIR and Mass Spectrometry

Forensic analysis, food science, pharmaceuticals, environmental monitoring, and analytical chemistry all face the fundamental difficulty of accurately separating and identifying volatile and semi-volatile chemicals. Because to its great separation efficiency and adaptability, gas chromatography (GC) is generally considered a dependable option [1]. Conventional GC detectors with low molecule specificity, such thermal conductivity detectors (TCD) or flame ionisation detectors (FID), offer quantitative data. Hyphenated techniques have become more popular in response to this; they combine GC with spectroscopic detectors, such as Fourier-transform infrared spectroscopy (FTIR) and mass spectrometry (MS), to provide information on chemical structure and separation [2,3].

In contemporary labs, GC-MS is by far the most often used hyphenated GC technology.  Through fragmentation patterns and library matching, it provides excellent sensitivity and selectivity and facilitates complicated sample analysis and structural elucidation.  Both focused quantification and thorough non-targeted screening are made possible by sophisticated instruments, such as quadrupole ion traps, time-of-flight (TOF), and accurate-mass platforms [4]. By recording the vibrational "fingerprints" of molecules, GC-FTIR, on the other hand, enhances MS and is particularly useful for differentiating isomeric compounds that fragment similarly in MS [5]. Recent developments, such light-pipe interfaces and cryogenic deposition techniques, have enhanced its analytical performance despite its traditionally lower sensitivity, reigniting interest in its application for structural confirmation tasks [5].

Innovations such as cloud-based data analytics, integrated multi-detectors (such as IR or photoionisation detectors), and portable GC–MS systems with microfabricated components are examples of how hyphenated techniques are still developing. Decision-making times in field or remote deployments are greatly shortened by these developments [6]. By automating data processing, machine learning and artificial intelligence (AI) are further improving capabilities and allowing for quick identification even in the absence of precise library matches [6].

Crucially, GC-FTIR offers vital supplementary capabilities, particularly in applications needing deep structural differentiation, even though GC-MS is still the gold standard because of its sensitivity and well-established libraries [6]. Both GC-MS and GC-FTIR are thoroughly evaluated in this study, which covers apparatus, interface designs, ionisation techniques, and their uses in forensic, environmental, food, and clinical studies. The future of hyphenated GC approaches is being guided by rising trends including portability, green workflows, and AI-driven data processing, all of which are highlighted in this paper.

2. Gas Chromatography – A Quick Overview

One essential analytical method for separating, identifying, and measuring volatile and semi-volatile substances is gas chromatography (GC).  When employing a liquid stationary phase (Gas–Liquid Chromatography, or GLC) or a solid stationary phase (Gas–Solid Chromatography, or GSC), it works on the concept of partitioning [7].

Several essential elements make up a standard GC setup:

• The injection port, which vaporises the material.
• An oven-housed column that contains a coated liquid stationary phase or a solid adsorbent; these are often fused-silica capillary columns, which provide good resolution because of their large surface area and tiny internal diameters [8].
• A detector that records analyte elution, such as FID, TCD, ECD, or MS.
• Chromatograms for analysis are generated using the data system [9].

Separation Mechanism: Analytes use volatility and affinity to divide between the stationary phase and the mobile phase, which is an inert gas such as helium.  Stronger interaction—caused by polarity or adsorption forces - elutes slowly, whereas more volatile chemicals elute more quickly [1].

1. The retention time (tR), which measures how long it takes a chemical to elute from the column and reach the detector, is one of the two crucial metrics employed in GC [9].
2. Selectivity (α) and retention factor (k) measure the strength of a compound's interaction with the stationary phase and the degree to which two compounds separate, respectively [10].

The Kovats Retention Index (RI) is frequently used to promote uniformity across tools and systems.  By using n-alkanes to normalise retention duration, it improves reproducibility and comparability of data, even in the face of changing operating circumstances [11,12]. High separation efficiency, rapidity, repeatability, and defined techniques are some of GC's benefits.  However, GC requires analytes to be volatile and thermally stable; polar or non-volatile compounds often necessitate derivatization (e.g., silylation, acylation) to improve volatility and peak shape [13,14]. GC is used in a wide range of applications, including the analysis of complicated forensic traces, volatile organic compounds (VOCs) in environmental samples, flavour and aroma chemicals in food, and metabolic wastes in clinical diagnostics.  The integration of GC with sensitive detectors, particularly MS, enhances identification and quantification capabilities [8,12].

3. Gas Chromatography–Mass Spectrometry (GC–MS)

3.1 Principle and Historical Context

Through mass-to-charge analysis, gas chromatography–mass spectrometry (GC–MS) combines the selectivity of mass spectrometry (MS) with the high-resolution separation capacity of GC. The combination of GC and MS in the middle of the 1950s set the stage for regular, data-rich analysis across a variety of fields. Commercial equipment and large spectrum libraries, such those from NIST and Wiley, made GC-MS a common technique in forensic labs, food analysis, medicines, and environmental monitoring [15].

3.2 Ionization Methods

The most common ionisation method in GC-MS is electron ionisation (EI), which operates at around 70 eV.  Although it frequently compromises molecular-ion visibility, this "hard" approach produces repeatable fragmentation spectra that are essential to library-based chemical identification [16]. Using reagent gases (such as methane or ammonia) to create protonated or adduct ions, Chemical Ionisation (CI) is a "soft" substitute that helps determine molecular weight and preserves more molecular ion information, especially in cases when EI is unable to synthesise an entire molecular ion [17]. For improved identification fidelity, recent developments include the use of TOF analysers for parallel EI/CI in a single run, which provides complementary ion populations in a single chromatographic event [18].

3.3 Mass Analyzers and Acquisition Modes

Due to their durability, affordability, and versatility in operating modes - which enable both full-scan and selected-ion monitoring (SIM) for flexible targeted or untargeted analysis -quadrupole (Q) analysers continue to be the workhorse in GC–MS [19]. Multi-stage mass spectrometry (MS) is made possible by Ion Trap (IT) equipment, which provide comprehensive structural fragmentation data that is useful for intricate analyte characterisation. Time-of-Flight (TOF) and Quadrupole-TOF (Q-TOF) devices improve untargeted screening procedures and facilitate retrospective data mining by providing high-resolution, accurate-mass data at rapid scan rates [20].  Significantly, GC-Q-TOF-MS has shown useful in environmental toxicity and designer steroid screening, offering quick inclusion of novel targets and screening without predefined analyte lists [21].

1. 4. Types of GC–MS Systems (Use Cases)

Single Quadrupole GC-MS: Frequently used in routine analytics for SIM-based quantification of volatile substances as well as full-scan screening. Triple Quadrupole GC–MS/MS (QqQ): This method uses SRM/MRM transitions to provide excellent selectivity and sensitivity, making it perfect for trace-level measurement in clinical toxin analysis and pesticide residue [8]. GC-MS Systems with High-Resolution Accurate Mass (HRAM) (such as Orbitrap and Q-TOF):  enable thorough, high-fidelity identification of unknowns and metabolites; they are becoming more and more popular for environmental non-targeted screening and metabolomics [20,21].

4. Gas Chromatography–Fourier Transform Infrared Spectroscopy (GC–FTIR)

4.1 Rationale

Due to their comparable fragmentation patterns, GC-MS may have trouble distinguishing between regioisomers and positional isomers, despite its superior sensitivity and library-based identification capabilities.  By detecting vibrational fingerprints, which are distinct infrared absorption bands linked to chemical bonds, GC-FTIR provides a convincing solution. This allows for orthogonal confirmation of molecular structure, especially in isomer discrimination [22].  Dispersive IR was used in early GC-FTIR systems, but performance and adaptability were greatly improved with the switch to interferometer-based FTIR (beginning in the late 1960s) [23].

4.2 Interfaces

There are three main categories of GC-FTIR interfaces:

Light-Pipe (LP): A heated gas cell that flows through and allows GC effluent to enter the infrared beam directly.  Although it has greater detection limits and restricted sensitivity, usually in the nanogramme range per component, it enables real-time, non-destructive vapor-phase spectra collecting [24]. Matrix Isolation (MI): GC effluent is cryogenically confined in an argon matrix (for example, by using gold-coated cryodisks at temperatures of around 12 K).  This greatly increases sensitivity over LP by concentrating analyte bands and producing crisper, higher-signal spectra [23]. Direct-Deposition (Cryo-Deposition): After the GC effluent is placed on a cold surface (such as 77 K), it is then examined using infrared technology.  In comparison to LP, this technique also provides improved sensitivity and spectral resolution [23,24].

There are trade-offs: although MI and direct deposition provide significantly higher sensitivity (up to two orders of magnitude), albeit through a two-step procedure (collection followed by analysis), LP provides simplicity and real-time analysis [23].

4.3 Applications

When structural specificity is essential, GC-FTIR is very useful, particularly for differentiating isomers or recognising restricted chemicals like illegal narcotics or new psychoactive substances.  In these situations, its capacity to offer unambiguous vibrational signals boosts analytical confidence [23].  Although they are smaller than mass spectral libraries, the extensive vapor-phase IR spectral libraries available for FTIR have great instrument repeatability [24]. To verify geographical origin or identify adulteration, GC-FTIR is also used in food and essential oil analysis, frequently in conjunction with chemometrics.  In order to uncover subtle chemical patterns, FTIR vibrational data is used in conjunction with GC separation and statistical modelling [25].

5. Sample-Introduction Strategies That Pair Well with GC–MS/GC–FTIR

A key factor in GC-MS and GC-FTIR performance is effective sample introduction, especially for trace-level analytes in complicated matrices.  Modern procedures today frequently use a number of solvent-free and enrichment-based approaches, including headspace sampling, purge and trap (P&T), solid-phase microextraction (SPME), stir-bar sorptive extraction (SBSE), and thermal desorption (TD).

5.1 Headspace Techniques (Static and Dynamic)

Static Headspace (HS): Before a predetermined volume is fed into the GC, volatile analytes equilibrate into the vapour phase and samples are sealed in vials.  This method is used in regular volatile analysis and quality control because it is easy to use and reduces matrix interferences. Analytes are purged from the sample into an adsorbent trap by an inert gas (usually nitrogen or helium) in the Dynamic Headspace / Purge and Trap (P&T) process. The analytes are then thermally desorbed into the GC.  According to U.S. EPA 524/8260 guidelines, P&T is frequently used in environmental monitoring, such as for volatile organic compounds (VOCs) in drinking water, and it increases sensitivity to the ppt level [26-30].  The method enhances detection limits and lessens water interference in GC–FTIR and GC–MS procedures.

5.2 Solid-Phase Microextraction (SPME)

A coated fibre (such as polydimethylsiloxane or PDMS) is used in SPME to directly absorb or adsorb analytes from liquid or headspace matrices, which are then thermally desorbed in the GC inlet.  It is economical, solvent-free, and automation-compatible.  Because of its quick extraction kinetics and repeatability, SPME has been popular in clinical bioanalysis, environmental VOC monitoring, and food aroma profiling [31].

5.3 Stir-Bar Sorptive Extraction (SBSE)

By employing a stir bar covered with a thicker PDMS layer, SBSE builds upon SPME and can increase analyte capacity by up to 100 times. For ultra-trace examination of semi-volatile organics in soil and water, it is particularly helpful. SBSE has outstanding sensitivity for both polar and nonpolar analytes when used in conjunction with thermal desorption GC-MS [31].

5.4 Thermal Desorption (TD)

VOCs are captured by thermal desorption (TD) on sorbent tubes (such as Tenax TA), which are then heated to release concentrated analytes into the GC.  In addition to supporting high-throughput operations and avoiding solvents, it is especially effective for environmental screening, forensic toxicology, and occupational air monitoring [32].

5.5 Comparisons and Workflow Compatibility

GC-MS is a very flexible method that is applied in many different fields.

Toxicology and environmental monitoring: GC-MS makes it possible to identify wastewater toxins, persistent organic pollutants, and volatile organic compounds (VOCs). It is essential for trace-level analysis and regulatory compliance because to its great sensitivity and resilience [26].

Forensic science: In forensic contexts, the method is frequently considered the "gold standard" for verifying the presence of toxicants, narcotics, explosives, and fire accelerants. Legal defensibility is supported by its repeatability and specificity [26]. Case backlogs in forensic labs have been greatly reduced by recent developments, such as quick GC-MS procedures, which have reduced run durations from about 30 minutes to about 10 minutes [27].

Food, drinks, and flavours: GC-MS is frequently used to help with authenticity testing, adulterant detection, and flavour profiling by characterising esters, terpenes, aldehydes, and pesticide residues [28–30].

Clinical and health sciences: Uses include metabolomics for elucidating disease pathways, VOC-based diagnostics in breathomics, and organic acid profiling for newborn screening for inborn metabolic abnormalities [26,31].

Complex biological matrices: Recent research has demonstrated that GC-MS/MS can successfully identify phthalates, pesticides in breast milk, and medications in larvae and pupae, hence broadening its application in forensic entomology and biomonitoring [32].

GC-FTIR, on the other hand, has complimentary capabilities. It can distinguish between isomers (such as positional and regioisomers) using vibrational fingerprints, which gets around MS's limits when fragmentation patterns are too close [33]. High-resolution GC and FTIR together provide separation and conclusive structural information for forensic drug validation [33]. Other uses include the study of polymers, fatty acids, medicines, petroleum hydrocarbons, and essential oils, where structural clarification is crucial [34].

7. Advantages and Limitations: GC–MS vs GC–FTIR

1. 1. Advantages