Determination Of Response Factors Research Articles

Determination of Response Factors for Analytes Detected during Migration Studies, Strategy and Internal Standard Selection for Risk Minimization.

Migration studies are one of the few domains of pharmaceutical analysis employing wide-scope screening methodologies. The studies involve the detection of contaminants within pharmaceutical products that arise from the interaction between the formulation and materials. Requiring both qualitative and quantitative data, the studies are conducted using Liquid Chromatography or Gas Chromatography coupled to a mass spectrometer (LC-MS and GC-MS). While mass spectrometry allows wide-scope analyte detection and identification at the very low Analytical Evaluation Threshold (AET) levels used in these studies, MS detectors are far from "universal response" detectors. Regulation brings the application of uncertainty factors into the picture to limit the risk of potential analytes detected escaping report and further evaluation; however, whether the application of a default value can cover any or all relevant applications is still debatable. The current study evaluated the response of species usually detected in migration studies, generating a suitable representative sample, analyzing said species, and creating a strategy and evaluation mechanism for acceptable classification of the detected species. Incorporating novel methodologies, i.e., Design of Experiments (DoE) for Design Space generation, the LC-MS-based methodology is also evaluated for its robustness in changes performed.

Non-aqueous reversed phase liquid chromatography with charged aerosol detection for quantitative lipid analysis with improved accuracy

There is a great need for efficient analysis of the composition of vegetable oils and fats, since it affects the physical and technical properties. However, due to the complex nature of these kind of samples, it is often difficult and costly. In the present study, we developed a Non-Aqueous Reversed-Phase HPLC method that can be used to separate and quantify different free fatty acids, fatty acid esters, monoacylglycerides, diacylglycerides and triacylglycerides, including regioisomers such as SOS/SSO and 1,2- and 1,3-diolein. Two 25 cm Nucleodur C18 Isis columns in series, sub-ambient column temperature and a mobile phase gradient composed of acetonitrile, acetic acid, isopropanol and heptane were used for the separation. The lipids were detected and quantified using a charged aerosol detector and it was found that the peak shape highly affected the detector response as well as the response uniformity, even when inverse gradient compensation was employed. Thus, calibration and determination of response factors were necessary for reliable quantification. A correlation between response factors and peak width at half peak height was found and used for quantification of non-calibrated components. A quantification approach was suggested including an appropriate selection of calibrated components, depending on sample composition and the accuracy required. It was shown in a complex oil sample that the reduced calibration approach, using only 6 instead of 33 calibrated components, resulted in virtually the same composition, but yielded a more accurate result compared to using relative area that neglects response factors. The method validation showed good reproducibility and accuracy, making it an excellent tool for extensive analysis of complex lipid mixtures.

Quantitative response in ion mobility spectrometry with atmospheric pressure chemical ionization in positive polarity as a function of moisture and temperature

Response of an ion mobility spectrometer at ambient pressure was quantitatively determined for fourteen chemicals from five chemical families spanning a range of proton affinities and temperature from 30 to 175 °C with moisture from 1 to 1 × 104 ppmv in purified air. Peak intensities, drift times and reduced mobility coefficients were determined for hydrated protons from a63Ni ion source and for protonated monomers and proton bound dimers of alcohols, aldehydes, acetates, ketones, and organophosphates. These measurements permitted the determination of response factors with atmospheric pressure chemical ionization and the influence of moisture and temperature on APCI response with correlation to computational models of hydration values. The formation of protonated monomers and proton bound dimers was described by heats of formation for a displacement reaction of water on H+(H2O)n by an analyte vapor and favorably matched results from density functional theory (DFT) with the 6-311 + G(dp) basis set. Response factors worsened with increased moisture and decreased temperature for compounds of medium, and more so, of low proton affinities. Findings here provide a broad measure and understanding for quantitative response in ion mobility spectrometers for substances for combinations of moisture and temperature.

A gas chromatograph for quantification of peroxycarboxylic nitric anhydrides calibrated by thermal dissociation cavity ring-down spectroscopy

Abstract. The peroxycarboxylic nitric anhydrides (PANs, molecular formula: RC(O)O2NO2) can readily be observed by gas chromatography (PAN-GC) coupled to electron capture detection. Calibration of a PAN-GC remains a challenge, because the response factors differ for each of the PANs, and because their synthesis in sufficiently high purity is non-trivial, in particular for PANs containing unsaturated side chains. In this manuscript, a PAN-GC and its calibration using diffusion standards, whose output was quantified by blue diode laser thermal dissociation cavity ring-down spectroscopy (TD-CRDS), are described. The PAN-GC peak areas correlated linearly with total peroxy nitrate (ΣPN) mixing ratios measured by TD-CRDS (r > 0.96). Accurate determination of response factors required the concentrations of PAN impurities in the synthetic standards to be subtracted from ΣPN. The PAN-GC and its TD-CRDS calibration method were deployed during ambient air measurement campaigns in Abbotsford, BC, from 20 July to 5 August 2012, and during the Fort McMurray Oil Sands Strategic Investigation of Local Sources (FOSSILS) campaign at the AMS13 ground site in Fort McKay, AB, from 10 August to 5 September 2013. The PAN-GC limits of detection for PAN, PPN, and MPAN during FOSSILS were 1, 2, and 3 pptv, respectively. For the Abbotsford data set, the PAN-GC mixing ratios were compared, and agreed with those determined in parallel by thermal dissociation chemical ionization mass spectrometry (TD-CIMS). Advantages and disadvantages of the PAN measurement techniques used in this work and the utility of TD-CRDS as a PAN-GC calibration method are discussed.

Practical Approach for the Determination of Response Factors of Impurities in Drugs by HPLC

For the determination of accurate quantity of impurities in the samples authentic impurity standards or response factors at a given wavelength must be known. In the presented work a convenient method for determination of relative response factors of impurities has been described without using an authentic impurities standard. An approach for the determination of response factors of the impurities where impurity standard is physically not available was developed and verified using different approaches. One such method was developed and verified by RP‐HPLC using Cosmosil C18 MS‐II column at UV 238 nm. Two different approaches were employed and the verification of correctness of approach was done using a known related substance of known response factor.

Detection and determination of p-coumaroylated units in lignins.

The derivatization followed by reductive cleavage (DFRC) method cleaves alpha- and beta-ethers in lignins but leaves lignin gamma-esters intact. When applied to grasses, which contain p-coumarate esters on their lignins, esterified monolignol derivatives are released. Saturation of the p-coumarate double bond occurs during DFRC, so the released products are 4-acetoxycinnamyl 4-acetoxyphenylpropionates. Synthesis of the esters allowed determination of response factors for the released products. Maize and bamboo lignins released 221 and 38 micromol/g of p-coumarate-derived esters. The sinapyl ester was much more abundant than the coniferyl one. The bamboo and maize lignin S/G ratios in the conjugates were 12 and 38 times greater than those of the normal monomers released by DFRC, evidence of a strong selectivity for acylation of syringyl units. Of three possible biochemical mechanisms for incorporating p-coumarates into lignin, evidence is mounting that the process involves incorporation of preacylated monolignols into the normal lignification process.

Quantitation in liquid chromatography of polymers: size-exclusion chromatography with dual detection

The problem of quantitation in size-exclusion chromatography (SEC) of polymers and oligomers is discussed, and a strategy for finding an appropriate combination of detectors and mobile phases for a given type of copolymer is described. This approach comprises the determination of response factors of different detectors for each homopolymer, and a simulation of dual detector SEC. The reliability of results is evaluated by analysis of homopolymers, polymer mixtures and copolymers of methyl methacrylate, ethylene oxide and dimethyl siloxane. Monodisperse fatty alcohol ethoxylates are used as models for block copolymers.

Rapid determination of response factors for the gas chromatographic thermal conductivity detector

Rapid determination of response factors for the gas chromatographic thermal conductivity detector

Gas-liquid chromatographic study and estimation of several urinary aromatic acids

A procedure for the separation of urinary acids as trimethylsilyl ethermethyl ester and methyl ester derivatives by temperature-programed gas chromatography has been developed. The liquid phase is 10% F-60. The excretion level of individual acids may be measured quantitatively after determination of response factors for the derivatives. A solvent extraction isolation procedure is suitable for aromatic compounds; nonaromatic compounds are extracted reproducibly but not quantitatively. Since the present method leads to derivatives of glucuronides and other nonaromatic acids in addition to aromatic acids, it provides a way of observing a pattern or profile of metabolic relationships that covers a wide range of compounds. Alterations in these patterns may result from environmental change, drug administration, or pathologic circumstances, and in these instances it may be more important to study over-all changes than to estimate several specific compounds. The determination of selected compounds and an analysis of pattern changes (without determination of response factors) can be made from the same chart, so that both qualitative and quantitative observations are obtained for each experiment. The method is being used in studies of drug effects, and for a study of developmental biochemistry for the neonate. The method may also be useful in studies of comparative biochemistry.