Sample Introduction Technique Research Articles

Development of Gas-Phase Sample-Introduction Techniques for Analytical Atomic Spectrometry

For the last 30 years, several types of gas-phase sample-introduction methods in analytical atomic spectrometry, i.e., atomic absorption spectrometry (AAS), atomic emission spectrometry (AES) and atomic fluorescence spectrometry (AFS), have been investigated and developed in the author's laboratory. Their fundamental results are summarized in this review article. The gas-phase sample-introduction techniques developed in the author's laboratory can be roughly divided into four groups: i) hydride generation, ii) cold-vapor generation of mercury, iii) analyte volatilization reactions and iv) miscellaneous. The analytical figures of merit of the gas-phase sample-introduction methods have been described in detail. Hydride generation has been coupled with the AAS of As, Bi, Ge, Pb, Sb, Se, Sn and Te, with the inductively coupled plasma (ICP) AES of As, Bi, Sn, Se and Sb, with the high-power nitrogen microwave-induced plasma (N2-MIP) AES of As, Bi, Pb, Sb, Se, Sn and Te by their single- and multi-element determinations, with the AFS of As, Bi, Pb, Sb, Se, Sn and Te, and with the ICP mass spectrometry (MS) of As and Se. The cold-vapor generation method for Hg has been combined with atmospheric-pressure helium microwave-induced plasma (He- or Ar-MIP)-AES and AFS. Furthermore, analyte volatilization reactions have been employed in the ICP-AES of iodine, in the He-MIP-AES of iodine bromine, chlorine, sulfur and carbon, and in the ICP-MS of sulfur. As a result, when compared with conventional solution nebulization, a great improvement in the sensitivity has been attained in each instance. In addition, the developed techniques coupled with analytical atomic spectrometry have been successfully applied to the determination of trace elements in a variety of practical samples.

Electrothermal vaporization in inductively coupled plasma atomic emission spectrometry for direct multielement analysis of food samples with slurry sampling

Slurry sampling followed by electrothermal vaporization (ETV) was used as sample introduction technique in inductively coupled plasma atomic emission spectrometry (ICP-AES) for the direct determination of trace elements in food samples. A polytetrafluoroethylene (PTFE) emulsion was used as a fluorinating reagent to promote vaporization and the transportation of analytes. The main factors affecting the analytical signals were investigated in detail. Under optimum operating conditions, the detection limits (DL) for this method varied from 1.8 (Cu) to 215 ng/mL (Zn), while the relative standard deviations (RSD) were in the range 2.6% (Cu)-7.2% (Zn). The proposed method was successfully applied to the direct determination of trace amounts of V, Cu, Cr, Fe, Zn, and La in rice without any chemical pretreatment. The precision was evaluated by analyzing a standard reference material (tea leaves, GBW 07605) and comparing the results from this method with results obtained by pneumatic nebulization (PN) ICP-AES after the wet-chemical decomposition of the same sample.

Molecular and compound-specific isotopic characterization of monocarboxylic acids in carbonaceous meteorites

Low molecular weight monocarboxylic acids are the most abundant water soluble organic compounds in the Murchison and many other CM type carbonaceous chondrites. In this study, we examined the monocarboxylic acids in Murchison and EET96029.20 carbonaceous meteorites using a new sample preparation and introduction technique for gas chromatograph recently developed for volatile, water-soluble organic compounds: solid phase micro-extraction (SPME). We identified more than 50 monocarboxylic acids from Murchison compared with the 18 compounds reported previously. Formic acid, a known interstellar molecule, has been fully analyzed in these carbonaceous meteorites, with its δD value suggesting an interstellar origin. We determined both carbon and hydrogen isotopic ratios of individual monocarboxylic acids in Murchison, to better define the origins and genetic relationships of these compounds. The compound-specific isotopic data reveal a large enrichment in 13C (δ 13C up to + 32.5 ‰) and particularly D (δD up to + 2024 ‰). The branched acids are substantially enriched in both 13C and D relative to the straight chain acids, with those branched acids containing a quaternary carbon showing the greatest isotopic enrichment. The isotopic difference may be attributed to variations in the different synthetic regimes or terrestrial input of straight chain acids.

Improved detection of low vapor pressure compounds in air by serial combination of single-sided membrane introduction with fiber introduction mass spectrometry (SS-MIMS-FIMS)

The use of two methods in tandem, single-sided membrane introduction mass spectrometry (SS-MIMS) and fiber introduction mass spectrometry (FIMS), is presented as a technique for field analysis. The combined SS-MIMS-FIMS technique was employed in both a modified commercial mass spectrometer and a miniature mass spectrometer for the selective preconcentration of the explosive simulant o-nitrotoluene (ONT) and the chemical warfare agent simulant, methyl salicylate (MeS), in air. A home-built FIMS inlet was fabricated to allow introduction of the solid-phase microextraction (SPME) fiber into the mass spectrometer chamber and subsequent desorption of the trapped compounds using resistive heating. The SS-MIMS preconcentration system was also home-built from commercial vacuum parts. Optimization experiments were done separately for each preconcentration system to achieve the best extraction conditions prior to use of the two techniques in combination. Improved limits of detection, in the low ppb range, were observed for the combination compared to FIMS alone, using several SS-MIMS preconcentration cycles. The SS-MIMS-FIMS response for both instruments was found to be linear over the range 50 to 800 ppb. Other parameters studied were absorption time profiles, effects of sample flow rate, desorption temperature, fiber background, memory effects, and membrane fatigue. This simple, sensitive, accurate, robust, selective, and rapid sample preconcentration and introduction technique shows promise for field analysis of low vapor pressure compounds, where analyte concentrations will be extremely low and the compounds are difficult to extract from a matrix like air.

Structural features of laser ablation particulate from Si target, as revealed by focused ion beam technology

Heterogeneity in laser-induced particle structures was investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) of individual particles micro-machined using focused ion beam (FIB). The primary particle size distribution spanned over three orders of magnitude, i.e., in the range 10 nm–10 μm with few larger secondary objects. The particulate larger than 0.5 μm often resulted from particle–particle aggregation, mostly upon a spherical core, seldom in chain-like structures. The core of these fractal aggregates was found to be polycrystalline. The heterogeneity of the particles with respect to structure and chemistry is surely of importance for elemental analysis using laser ablation as sample introduction technique.

On-line introduction of high-pressure gas–liquid sample for capillary gas chromatographic analysis

An on-line sample introduction technique in capillary gas chromatograph (CGC) for the analysis of high-pressure gas–liquid mixtures has been designed and evaluated. A sample loop of 0.05 μL and a washing solvent loop of 0.5 μL are mounted on a 10-port switching valve, which serves as the injection valve. A capillary resistor was connected to the vent of sample loop in order to maintain the pressure of the sample. Both the sample and the washing solvent are transferred into the split-injection port through a narrow bore fused silica capillary inserted into the injection liner through a septum. The volume of the liner is used both as the pressure-release damper and evaporation chamber of the sample. On-line analysis of both reactants and resultants in ethylene olimer reaction mixture at 5 MPa was carried out, which demonstrated the applicability of the technique.

Static headspace versus head space solid-phase microextraction (HS-SPME) for the determination of volatile organochlorine compounds in landfill leachates by gas chromatography

The determination of five volatile organochlorine compounds, VOX (chloroform, 1,1,1-trichloroethane, carbon tetrachloride, trichloroethene and tetrachloroethene) in raw landfill leachates and biologically cleansed leachates by GC-MS is investigated. Two extraction and preconcentration procedures were evaluated for recovery of such analies from the samples, including static headspace (HS) and solid phase microextraction by sampling the headspace above the sample (HS-SPME). Optimisation of operating parameters for the best performance of both, sampling and preconcentration techniques was described. Detection limits, time of analysis, precision and linear ranges of both introduction techniques have been established. Application of proposed methods to the determination of the five VOX under study in the above referred samples revealed the absence of such analytes in both leachates. Then both methods were applied to the determination to the five organochlorine compounds under study on spiked leachates samples. While HS-GC-MS offered better analytical precision than HS-SPME-GC-MS, this last technique gave a faster analytical response because no dilution must be done for a reliable VOX determination in landfill leachates. In any case, both sample introduction techniques tested provides excellent recoveries and good analytical precision (ranged from 1 to 3%).

Interlaboratory evaluation of injection techniques for triglyceride analysis of cocoa butter by capillary gas chromatography

As part of two international collaborative studies, in which 14 laboratories applied capillary GLC to determine the triglyceride (TG) profile of cocoa butter, the performance of different sample introduction techniques, i.e. cold on-column injection (OCI), split injection and programmed-temperature vapouriser (PTV) injection, was compared. In both studies, the participants did not apply a uniform GLC procedure. Synthetic mixtures of triglycerides were chosen to permit an accurate determination of detector response factors. No statistically significant difference was found between the mean values obtained by different injection modes. The OCI, generally recommended as best practice, did not give superior results than the PTV or the split injection techniques.

Isotopic analysis of Fe in human red blood cells by multiple collector-ICP-mass spectrometry.

Precise 56Fe/54Fe and 57Fe/54Fe isotopic ratios on human red blood cell (RBC) samples have been measured using multiple collector-ICP-mass spectrometry (MC-ICPMS). The mass spectrometric interferences on Fe isotopes (e.g., 56ArO+ and 57ArOH+) were successfully minimized by a dry plasma condition achieved by a desolvating nebulizer sample-introduction technique. In order to eliminate possible variations in the measured isotopic ratios due to non-mass spectrometric interferences, Fe was separated from remaining organic compounds and major co-existing elements using an ion chromatographic technique. The resulting precisions of the 56Fe/54Fe and 57Fe/54Fe ratio measurements were 0.12 per thousand and 0.20 per thousand, respectively, which were high enough to detect the isotopic variation of Fe in nature. For an interlaboratory comparison, all of the Fe isotopic ratio data were normalized by the ratios for the IRMM-014 international isotopic standard. A series of 12 RBC samples were collected from one person through monthly-based sampling over a period of one year. These were analyzed to test possible seasonal changes in the 56Fe/54Fe and 57Fe/54Fe ratios. Moreover, in order to test possible variations in the 56Fe/54Fe and 57Fe/54Fe ratios among different people, RBC samples were collected from five volunteers (four males and one female). The 56Fe/54Fe and 57Fe/54Fe ratios for a series of 12 RBC samples collected over a one-year period show 3.06 per thousand and 4.51 per thousand lower than the values of IRMM-014, and no significant seasonal change could be found in the ratios. The lack in seasonal changes in the Fe isotopic ratios could be explained by a small contribution of the daily net-intake of Fe (1 - 2 mg/day) onto the total amount of Fe in the human body (2 - 4 g). The 56Fe/54Fe and 57Fe/54Fe ratios for RBC samples collected from four male samples did not vary measurably, whereas the Fe isotopic ratios for a female RBC were 0.3 per thousand/amu heavier than the mean value of four male samples. This difference in Fe isotopes among the individuals can be the result of a difference in uptake efficiency of the Fe through a dietary process from the digestive tract. The data obtained here demonstrate that the isotopic ratios of trace metals can provide new information about metabolic efficiencies of the metallic elements.

Static headspace versus head space solid-phase microextraction (HS-SPME) for the determination of volatile organochlorine compounds in landfill leachates by gas chromatography

The determination of five volatile organochlorine compounds, VOX (chloroform, 1,1,1-trichloroethane, carbon tetrachloride, trichloroethene and tetrachloroethene) in raw landfill leachates and biologically cleansed leachates by GC-MS is investigated. Two extraction and preconcentration procedures were evaluated for recovery of such analies from the samples, including static headspace (HS) and solid phase microextraction by sampling the headspace above the sample (HS-SPME). Optimisation of operating parameters for the best performance of both, sampling and preconcentration techniques was described. Detection limits, time of analysis, precision and linear ranges of both introduction techniques have been established. Application of proposed methods to the determination of the five VOX under study in the above referred samples revealed the absence of such analytes in both leachates. Then both methods were applied to the determination to the five organochlorine compounds under study on spiked leachates samples. While HS-GC-MS offered better analytical precision than HS-SPME-GC-MS, this last technique gave a faster analytical response because no dilution must be done for a reliable VOX determination in landfill leachates. In any case, both sample introduction techniques tested provides excellent recoveries and good analytical precision (ranged from 1 to 3%).

Characterisation of a hydraulic high-pressure sample introduction assisted flow injection—inductively coupled plasma time-of-flight mass spectrometry system and its application to the analysis of biological samples

A flow injection (FI) method was developed using hydraulic high-pressure nebulization as a sample introduction system, coupled to inductively coupled plasma time-of-flight mass spectrometer (ICP-TOFMS) for rapid and simultaneous determination of 19 elements. The operating conditions of the system (analyte flow rate, heating and cooling temperatures of the desolvation module, carrier gas flow rate) for the simultaneous determination of 19 analytes were optimised. The optimum parameters of the sample introduction system were found to be 1.4mlmin−1 and 1.35lmin−1 for the analyte solution and nebulizer flow rates, respectively. A compromised condition for heating and cooling stage temperatures of 170 and −5°C was chosen. The detection limits were compared to those obtained by using ICP-TOFMS with alternative sample introduction techniques e.g. conventional nebulization, flow injection chemical hydride generation (FI-CHG) and the obtained results were comparable or better than those resulting from alternative sample introduction. Applying the optimised conditions the simultaneous determination of Ag, As, Ba, Cd, Co, Cu, Ga, In, Li, Mn, Mo, Pb, Sb, Se, Sn, Sr, Tl, V and Zn was carried out. Absolute detection limits (3σ) in the range of 2–750pg and precision between 0.5 and 9.6% from five replicate measurements of 10ngml−1 multielemental sample solutions were achieved by using a 200μl sample loop. The developed method was applied for the analysis of certified reference materials of biological origin (TORT-2 “Lobster Hepatopancrease”, BCR-422 “Cod Muscle” and IAEA MA-B-3/TM “Fish Homogenate”), and the results showed good agreement with the certified values.

Determination of cadmium in polyethylene by analytical atomic spectrometry with gas-phase sample introduction technique

Cadmium in polyethylene was determined by both inductively coupled plasma atomic emission spectrometry (ICP-AES) and atomic absorption spectrometry (AAS) with continuous-flow gas-phase sample introduction in a reaction medium of ascorbic acid. In the presence of mixture of cobalt and thiourea in the ascorbic acid solution, the sensitivities by both ICP-AES and AAS for cadmium were greatly enhanced. The gaseous cadmium species was phase-separated in a gas–liquid separator and directed via a stream of argon carrier gas to an inductively coupled plasma and an electrically heated quartz tube atomizer (QTA) for atomic spectrometry. Under the optimized experimental conditions, the best attainable detection limits at Cd I 228.802 nm line were 1.3 and 0.017 ng/ml with linear dynamic ranges of 10–500 ng/ml and 0.1–1 ng/ml in concentrations by ICP-AES and QTA-AAS, respectively. The instrumental precisions expressed as the relative standard deviation (R.S.D.) from ten replicate measurements of 50 and 1 ng/ml cadmium by ICP-AES and QTA-AAS were 5.6% and 3.2%, respectively. With the use of ICP-AES and QTA-AAS with gas-phase sample introduction method, six- and 200-fold improvements in detection limits for cadmium were obtained in comparison with their conventional solution nebulization methods, respectively. After the effects of several diverse elements on the determination of cadmium by ICP-AES and QTA-AAS with the present gas-phase sample introduction systems were examined, these methods were applied to the determination of low concentrations of cadmium in polyethylene. The results obtained by the present method were in good agreement with the certified values.

Determination of cadmium in polyethylene by analytical atomic spectrometry with gas-phase sample introduction technique

Cadmium in polyethylene was determined by both inductively coupled plasma atomic emission spectrometry (ICP-AES) and atomic absorption spectrometry (AAS) with continuous-flow gas-phase sample introduction in a reaction medium of ascorbic acid. In the presence of mixture of cobalt and thiourea in the ascorbic acid solution, the sensitivities by both ICP-AES and AAS for cadmium were greatly enhanced. The gaseous cadmium species was phase-separated in a gas–liquid separator and directed via a stream of argon carrier gas to an inductively coupled plasma and an electrically heated quartz tube atomizer (QTA) for atomic spectrometry. Under the optimized experimental conditions, the best attainable detection limits at Cd I 228.802 nm line were 1.3 and 0.017 ng/ml with linear dynamic ranges of 10–500 ng/ml and 0.1–1 ng/ml in concentrations by ICP-AES and QTA-AAS, respectively. The instrumental precisions expressed as the relative standard deviation (R.S.D.) from ten replicate measurements of 50 and 1 ng/ml cadmium by ICP-AES and QTA-AAS were 5.6% and 3.2%, respectively. With the use of ICP-AES and QTA-AAS with gas-phase sample introduction method, six- and 200-fold improvements in detection limits for cadmium were obtained in comparison with their conventional solution nebulization methods, respectively. After the effects of several diverse elements on the determination of cadmium by ICP-AES and QTA-AAS with the present gas-phase sample introduction systems were examined, these methods were applied to the determination of low concentrations of cadmium in polyethylene. The results obtained by the present method were in good agreement with the certified values.

Gas chromatography combined with fast flow glow discharge mass spectrometry (GC-FFGD-MS)

A low power (<5 W) dc fast flow glow discharge (FFGD) ion source has been adapted for the detection of halogenated hydrocarbons using gas chromatography as the sample introduction technique. A simple and robust interface design enabled direct coupling of the ion source to a common gas chromatograph. After optimisation, detection limits for four compounds were from 0.3–66.5 pg (by monitoring the halogen ions 35Cl, 79Br and 127I). The source operating conditions can be ‘tuned’ to obtain different information, allowing both sensitive elemental detection and structure elucidation using a single instrument, with sub-pg detection limits for the bromobenzene molecular ion. The source pressure, power and discharge gas flow rate were found to have significant effects on the relative fragment ions detected. These observations can be rationalised using neutral, excited state chemistry.

Sample introduction techniques for microfabricated separation devices

A great deal of progress has been made toward the development of the micro total analysis system (micro-TAS) since its inception in 1990. A wide variety of applications, including genomics, proteomics and drug discovery, have prompted the development of analytical methods capable of very high throughput while maintaining low cost. The micro-TAS concept addresses both of these requirements. Electrophoresis has been a key element in the development of the micro-TAS. Most chemical and biochemical assays utilize a separation component at some point during analysis. Genomics, in particular, depends almost exclusively on electrophoresis for size-based separations of DNA. This review examines sample introduction into microfabricated electrophoretic devices, or chips, primarily for DNA analysis. Sample introduction is an important component of these systems and is an essential process for making chip electrophoresis a widely applicable analytical technique. Specific issues, such as automation, the delivery of large numbers of samples to microfabricated devices and injection of picoliter-sized sample plugs into a separation lanes on chips, are presented.

レーザーアブレーション-誘導結合プラズマ質量分析法による地球化学試料の微量元素分析

This paper describes advances in elemental and isotopic ratio measurements that have been made with inductively coupled plasma mass spectrometry (ICP-MS) coupled with a laser-ablation sample introduction technique. Laser ablation utilizing UV light (frequency quadrupled to 266 nm or quintupled to 213 nm by a Nd-YAG laser, or an ArF Excimer 193 nm laser) is now the most widely used system because of its higher analytical precision and analytical capability to most of solid samples. However, even with UV lasers, serious elemental fractionation may occur during laser ablation, mainly due to differences in the element volatility. Therefore, the reduc- tion of elemental fractionation during ablation is necessary for further precise and accurate ele- mental and isotopic analyses of trace elements. This is particularly the case for high quality-iso- tope data for age determination. In the field of geochemistry, great efforts have been made to obtain accurate Pb/U ratios, because 206 Pb/ 238 U ratios provide chronological information. The basic problem is that Pb/U results using conventional LA-ICPMS techniques show serious frac- tionations of the ratio over a prolonged measurement. The observed Pb/U ratio increases dur- ing the measurement because of the greater volatility of Pb. The Pb/U elemental fractionation is successfully reduced by an active focus technique, chemically assisted-laser ablation technique, or by soft-ablation technique. Moreover, recently developed techniques including signal sta- biliser, a correction for the slow response of a Faraday amplifier and removal of isobaric interfer- ence by cool plasma conditions, will also expand the application fields and analytical accuracies of the LA-ICPMS technique. Outlines of these techniques are introduced.

Determination of metal impurities in titanium dioxide using slurry sample introduction by axial viewing inductively coupled plasma optical emission spectrometry

A slurry sample introduction technique for the analysis of TiO2 powders by axial viewing ICP-OES is reported. Relationships between stable slurries and the conditions, such as particle size, pH, dispersant and its amount, were experimentally investigated. Slurries were prepared by mixing the TiO2 powder with the dispersant poly(acrylate amine) (NH4PAA) and agitation in an ultrasonic bath to ensure good dispersion. The pH of the medium and amount of dispersant has been optimized. Impurities in TiO2 were determined by an axial viewing ICP-OES spectrometer. As representatives, a Standard Reference Material 154 b of µm particle size TiO2 and a nm particle size TiO2 were selected and determined for micro and trace impurities. Analytical results obtained via slurry sample introduction were compared with those via nebulization of aqueous solutions prepared by acid digestion and fusion digestion. The determined results by slurry introduction were in good accordance with the stated values, which verified that the calibration curves could be established by aqueous standards.

Tandem Mass Spectrometry in the Newborn Screening Laboratory

A common definition of newborn screening is “the presumptive identification of unrecognized congenital disorders by the application of laboratory tests to an entire population.” Newborn screening began in the 1950s, when Robert Guthrie developed a screening test for the metabolic disorder phenylketonuria (PKU) based on measuring the level of the amino acid phenylalanine in dried, whole blood specimens collected on filter paper. The immediate success prompted similar, mandated “PKU Screening” in all states by the mid-1960s. Subsequently, test methods were developed for other congenital or metabolic disorders including hypothyroidism, maple syrup urine disease, galactosemia, and biotinidase. The paradigm involved a separate test procedure for each disorder. In the 1990s, that paradigm radically changed with the introduction of tandem mass spectrometry (MS/MS) into the newborn screening laboratory. Tandem mass spectrometry is a technique which uses 1 blood spot specimen to detect a multiple of potential disorders. MS/MS in the Laboratory The MS/MS technologies for routine use in high production laboratories (ie, newborn screening laboratories) have evolved from liquid chromatography/mass spectrometer (LCMS) systems. The 1970s and 1980s saw several advances in mass spectrometry instrumentation that included improved sample introduction techniques such as fast atom bombardment (FAB) and fast ion bombardment (FIB). Also the development in the 1980s of quadrupole (4 magnetic rods) units, linking them in series, and controlling the function (separation, fragmentation, and detection) of each unit led to today’s tandem mass spectrometry systems. Concurrently, experimentation with sample preparation techniques improved sensitivity and reproducibility by incorporating procedures based on the formation of

Determination of carbon in aqueous solutions by atmospheric-pressure helium microwave induced plasma atomic emission spectrometry with gas-phase sample introduction technique.

A trace amount of carbon was determined by atmospheric-pressure helium microwave induced plasma atomic emission spectrometry (He-MIP-AES) with gas-phase sample introduction technique. This method was applied for the generation of a continuous flow of carbon dioxide by the acidification of carbonate ion and hydrogen carbonate ion for the determination of carbon. The generated carbon dioxide was separated from the solution by a simple gas-liquid separator, dried with a desiccant and swept into the MIP with helium carrier gas for analysis. Of the acids and drying agents investigated, hydrochloric acid for acidification and anhydrous calcium chloride as a desiccant were found to be the most appropriate for the generation of carbon dioxide. Under the optimized experimental conditions, the best attainable detection limits at C (I) 193.09 and C (I) 247.86 nm lines were 7.89 and 8.10 microg/l with linear dynamic ranges of 100 to 10,000 and 100 to 20,000 microg/l for carbon, respectively. The presence of many diverse elements and ions was found to cause a more or less depressing interference by the proposed technique. However, no interference was observed from the following elements and ions: Ca, K, Rb, Br-, Cl-, F- and I-. Finally, the present method has been applied to the determination of carbon in several water samples.

Residual solvent testing: a review of gas-chromatographic and alternative techniques.

The purpose of this brief review is to describe and discuss some of the current analytic procedures including gas-chromatographic and alternative techniques for residual solvent testing. Residual solvents, or organic volatile impurities, are a potential toxic risk for pharmaceutic products and have been a concern of manufacturers for many years. Residual solvents have had official limits in the United States as set in USP XXV and by the FDA in 1997 and have been monitored by most pharmaceutical manufacturers extensively for more than two decades in both bulk and finished products. The chief method of analysis for residual solvents is gas chromatography, which is generally considered the preferred methodology. Sample introduction techniques include both static and dynamic headspace analysis, solid-phase microextraction, and direct injection of solution containing bulk drug substance or drug product into the gas chromatograph. Also, some alternative methodologies for residual solvent testing are discussed in this review. In conclusion, gas chromatograph-based procedures will continue to dominate residual solvent testing because of its specificity for identification of the solvent, but the use of alternative sample introduction techniques into a gas chromatograph will continue to expand in the near future.