Extractable and Leachable (E&L) evaluations have become increasingly more vital to successful medical device product development and regulatory submissions. According to requirements and guidance from the US Food and Drug Administration (FDA), European Medicines Agency (EMA), ISO and the Product Quality Research Institute (PQRI)[1-4], E&L profiles should be established by exhaustive extraction with multiple solvents of varying polarities and reliable determination with distinctive analytical techniques.
Gas chromatography mass spectrometry (GC-MS) analysis with headspace (HS) or liquid injection detects volatile and semi volatile components in E&L studies. Due to the complexity of materials and the unpredictability of an E&L analysis, two-step analysis (initial screening and target analysis) is usually employed for qualification and quantification of compounds detected. This is a costly, time consuming and labor-intensive process.
The Polyarc®/FID system converts carbon atoms of organic molecules found in the column effluent into methane which then generates an FID response. The resulting detector response is uniform on a per carbon basis and allows the FID to have a truly universal carbon sensitivity. This eliminates the need for calibration standards for each identified compound to determine an internal or external standard’s response factor. Gas chromatography using full scan MS combined with parallel Polyarc®/FID detection could apply to E&L studies, integrating a two-step process into a one-step analysis.
Two XTI -5MS Columns were installed into the front inlet of a 6890 GCMS. One of the columns was connected to the 5975 Mass Spectrometer while the other was connected to the Polyarc® and FID. Two groups of known extractables and leachables of concern were prepared in acetone solutions at concentrations ranging from 50 µg/mL to 100 µg/mL. These preparations were spiked with a known volume of internal standard at a concentration of 25 µg/mL before triplicate analysis on the instrument. Calculation of the relative response factors of each analyte was performed with both the Mass Spectrometer and Polyarc®/FID data for comparison.
The flame ionization detector (FID) is widely used in the field of gas chromatography because it is highly sensitive to many organic compounds and provides a linear response over many orders of magnitude. However, FIDs suffer from two main drawbacks: the response to analytes are variable (and therefore require time-consuming calibration) and the FID provides low or no response to highly functionalized molecules such as carbon monoxide, carbon dioxide, formic acid, formaldehyde, and formamide. In this application note, we show that an FID equipped with a Polyarc reactor is not only highly sensitive to these compounds but also provides a response factor that is equivalent for all carbon-containing compounds, thus eliminating the need for time-consuming calibration. Compared to conventional FID-only systems, the Polyarc reactor eliminates the need for a second detector to quantify carbon monoxide and carbon dioxide, improves accuracy in quantitative analysis, and saves time and money associated with calibrations.
Quantification of unknowns with gas chromatography traditionally requires time-consuming and costly calibration steps including purchasing, preparing, and analyzing calibration standards, and applying the calibration results to determine analyte concentration. In this application note, we describe a method for identifying and quantifying unknowns in a single injection using a parallel Polyarc®/FID and mass spectrometer (MS).
ASTM D2163 (Standard test Method for Determination of Hydrocarbons in Liquefied Petroleum Gases and Propane/Propene Mixtures by Gas Chromatography) and ASTM D5501 (Standard Test Method for Determination of Ethanol and Methanol Content in Fuels Containing Greater than 20% Ethanol by Gas Chromatography) are routinely used in refinery laboratories. Both test methods require the use of response factors and were chosen to evaluate the effectiveness of the Polyarc system. As written test method ASTM D2163 gives users the option of using theoretical FID response factors or calculating response factors from the use of certified calibration standards. ASTM 5501 suggests typical mass response factors that are validated using multilevel calibration standards. Reported results for D2163 analysis are calculated using the theoretical response factors stated in the method relative to n-butane. Additionally, a demo “cryo sleeve” and updated “cryo block” were evaluated with the Polyarc reactor to allow the reactor to operate when cryogenic oven cooling is needed. The evaluation of ASTM D2163 was accomplished using a 150 meter column and cryogenic oven cooling. The GC conditions are listed below.
The Polyarc microreactor was used to quantify 2-acetyl-1-pyrroline (2AP) and 1-vinyl-2-pyrrolidone (1V2P) by gas chromatography (GC) analysis. Results were compared with internal standard quantification methods. The Polyarc microreactor reported comparable results when compared to traditional GC quantification techniques with the distinct advantage of not requiring a reference standard. Consequently, the Polyarc detector provided a more simple quantification instrumental setup that would also provide improved analysis of very complex extracts such as flavor solutions.
Utilizing the ARC Polyarc system and FID combination, hydrogen was evaluated as a carrier gas while investigating polar compounds known for potentially poor chromatographic peak shape and response factors. Compounds chosen were n-Decane, nOctanol, Aniline, m-Cresol, Triethyleneglycol (TEG), Catechol and n-Hexadecane. n-Decane and n-Hexadecane were included for comparison as more ideal compounds for chromatography and response factors. All compounds were treated as external standards between the levels of 0.2 – 5 weight % as carbon. Hydrogen (Air Liquide, Alphagaz1, 99.999% purity) was used as the column carrier gas to evaluate any potential effects on the reactor. All compounds showed good peak shape and the Polyarc/FID response factors between components narrowed significantly when compared to just FID response alone. In this study, no adverse effects where observed with hydrogen as the carrier gas. The small amount of hydrogen carrier flow kept the reactor conditioned while one could turn off the air/hydrogen to the reactor mass flow controller as well as the air to the FID during short standby periods.
The concentrations of oxygenates commonly used as fuel additives were determined with an average error of 1.7%, and within gravimetric uncertainties, using an ARC Polyarc reactor in series with a flame ionization detector (FID) on a gas chromatograph (GC). The analysis demonstrates a greater than 5-fold speed-up of analysis with less cost and less introduction of human error. This method is applicable to a wider range of volatile organic compounds (VOCs) that have importance in environmental and industrial testing.
An ARC Polyarc reactor was used in series with a flame ionization detector (FID) to analyze the composition of fatty acid methyl esters (FAMEs) in a mixture. By using this method, accurate quantification of 24 different FAMEs (C8 to C24) is demonstrated without the use of correction factors (response factors) and with a single internal standard (methyl tricosanoate) with an average error of 2.2%. The quantification error of C8 and C10 esters is significantly reduced compared with an analysis using FID and theoretical correction factors (from 9.7% to 5.6% and 3.1% to 0.3%, for C8 and C10, respectively). These results suggest that the accurate quantification of large mixtures of FAMEs is possible without calibration or theoretical correction factors because of the universal carbon response of the Polyarc/FID.
The quantification of pesticides in food using gas chromatography (GC) is traditionally a time-consuming process that involves the painstaking calibration of detector response for each analyte. The conversion of analytes to methane before their detection with a flame ionization detector (FID) results in a response that is proportional to the number of carbon atoms in the analytes and thereby eliminates the need for detector calibration. In this note, we use this approach and show the application of the Polyarc reactor to the quantification of dilute pesticides. The response factors of compounds in a commercial 22-component organochlorine pesticide mixture (200 µg/mL of each component) were 1.00 ± 0.09 with an average deviation from unity of 4%. This is compared to an FID-only analysis with response factors of 0.83 ± 0.10 with an average deviation from unity of 17%. Additional testing of the Polyarc reactor for six single-analyte pesticide solutions prepared from pure components provided response factors of 1.00 ± 0.04 with a mean deviation of 2%. Because all compounds have a response factor of one when using the Polyarc reactor, calibration to determine response factor is no longer required. We also show that direct-connect splitless liners prevent discrimination of analytes in the GC injector port.
The conversion of analytes to methane before their detection with a flame ionization detector (FID) using gas chromatography (GC) gives more uniform analyte response. In this application note, we use the Polyarc® reactor to convert C5 to C18 n-alkanes to methane in order to quantify their concentrations. The Polyarc® reactor allows for accurate quantification (average error of 0.9%) of the hydrocarbons studied here. The Polyarc® reactor maintains high separation efficiency with only a 9% increase in peak width compared to an FID-only analysis. We demonstrate that low inlet pressures can lead to discrimination in the vaporization of hydrocarbons in the inlet, especially those with large differences in boiling points, and we describe methods for the optimization of inlet conditions to avoid these issues.
Learn more about the Polyarc system from these peer-reviewed papers:
The flame ionization detector (FID) is a robust tool in gas chromatography (GC) due to its sensitivity and linear response in the detection of common organic compounds. However, FID response to oxygenated or highly functionalized organic molecules is low, or in some cases non-existent, making it difficult or impossible to detect and quantify some organic compounds. In this work, the combination of a GC/FID system with a catalytic microreactor, which performs post-column combustion-methanation to convert organic compounds to methane, is shown to be an effective approach for quantifying low-response organic compounds. Molecules that were previously undetectable by conventional FID, including carbon monoxide and carbon dioxide, respond with the same high response of methane in the FID. Low-response molecules, including formaldehyde, formic acid, formamide, and ten other oxygenates also demonstrated enhanced detector response equivalent to that of methane in the FID. The linear response of the FID to these molecules and the equivalent sensitivity to methane indicate that accurate quantification is possible without the usual calibration-corrections (e.g., response factors or correction factors) to the FID response.
Catalytic hydrogenation of itaconic acid (obtained from glucose fermentation) yields 3-methyl-tetrahydrofuran (3-MTHF), which then undergoes catalytic dehydra-decyclization to isoprene. It is demonstrated that a one-pot cascade reaction converts itaconic acid to 3-MTHF at ∼80% yield with Pd–Re/C catalyst and 1000 psig H2. Subsequent gas-phase catalytic ring opening and dehydration of 3-MTHF with phosphorus-containing zeolites including P-BEA, P-MFI, and P-SPP (self-pillared pentasil) exhibits 90% selectivity to dienes (70% isoprene, 20% pentadienes) at 20–25% conversion.
Analysis of trace compounds, such as pesticides and other contaminants, within consumer products, fuels, and the environment requires quantification of increasingly complex mixtures of difficult-to-quantify compounds. Many compounds of interest are non-volatile and exhibit poor response in current gas chromatography and flame ionization systems. Here we show the reaction of trimethylsilylated chemical analytes to methane using a quantitative carbon detector (QCD; the Polyarc™ reactor) within a gas chromatograph (GC), thereby enabling enhanced detection (up to 10×) of highly functionalized compounds including carbohydrates, acids, drugs, flavorants, and pesticides. Analysis of a complex mixture of compounds shows that the GC-QCD method exhibitsfaster and more accurate analysis of complex mixtures commonly encountered in everyday products and the environment.
American Laboratory:Calibration-Free Catalytic Microreactor for Analysis of Pesticides in Food (begins on pg. 21)