Cyanoacetohydrazide as a Novel Derivatization Agent for the Determination of UHPLC-HRMS Steroids in Urine.

The possibility of cyanoacetohydrazide usage as a novel derivatizing agent is demonstrated in the presented article, and a comparison with hydroxylamine as the most commonly used reagent is provided. Optimal conditions for steroid derivatization with cyanoacetohydrazide are provided. According to the collected data, the maximum yield of derivatives was observed at pH 2.8 within 70 min at 40 °C with 5 ng/mL limit of detection for all investigated analytes. It was shown that cyanoacetohydrazide derivatives produces both syn- and anti-forms as well as hydroxylamine, and their ratios were evaluated and shown in presented work. An efficiency enchantment from two to up to five times was achieved with a novel derivatization reagent. Its applicability for qualitative analysis of steroids in urine was presented at real samples. Additionally, the reproducible fragmentation of the derivatizing agent in collision-induced dissociation offers opportunities for simplified non-targeted steroidomic screening. Furthermore, cyanoacetohydrazide increases ionization efficiency in positive mode, which can eliminate the need for redundant high-resolution instrument runs required for both positive and negative mode analyses.

Selectivity comparison of acetonitrile-methanol-water ternary mobile phases on an octadecylsiloxane-bonded silica stationary phase.

The solvation parameter model was used in this study to investigate various intermolecular interactions that influence retention on the standard C18 stationary phase for the solvent system acetonitrile:methanol (ACN:MeOH, 1:1). In comparison to the organic mobile phase modifiers acetonitrile, acetone, methanol, 2-propanol, and tetrahydrofuran, the solvent strength for the ACN:MeOH (1:1) solvent system was evaluated. To facilitate the interpretation of various intermolecular interactions that contribute to retention on a standard C18 stationary phase for the solvent system ACN:MeOH (1:1), system maps were constructed and compared with those of acetone, tetrahydrofuran, acetonitrile, 2-propanol, and methanol. The solvation parameter models were constructed for the ternary solvent system ACN:MeOH (1:1)-water, and in the models constructed, the coefficient of determination values were from 0.998 to 0.999, the Fisher statistic values for the models were from 1687 to 4015, and the standard error of the estimate values ranged from 0.022 to 0.029. The solvent system ACN:MeOH (1:1) has retention properties more similar to methanol than acetonitrile, indicating methanol's influence is more dominant.

Phthalylglycyl Chloride as a Derivatization Agent for UHPLC-MS/MS Determination of Adrenaline, Dopamine and Octopamine in Urine.

Dopamine, adrenaline and octopamine are small polar molecules that play a vital role in regulatory systems. In this paper, phthalylglycyl chloride was proposed as a derivatization agent for octopamine, adrenaline and dopamine determination in urine for the first time. The derivatization procedure facilitated the use of reversed-phase liquid chromatography with positive electrospray ionization-high-resolution mass spectrometry. An LC-HRMS method was developed that provided quantification limits of 5 ng/mL and detection limits of 1.5 ng/mL for all analytes. The 95-97% yield of derivates was observed after a 10 min derivatization with phthalylglycyl chloride at pH 6.5 and 30 °C. The proposed method was successfully applied to the analysis of human urine samples. The obtained results were compared with those of conventional derivatization procedures with 9-fluorenyl-methoxycarbonyl chloride and dansyl chloride.

Retention properties of acetone-water mobile phases on a biphenylsiloxane-bonded silica stationary phase in reversed-phase liquid chromatography.

The solvation parameter model system constants and retention factors were used to interpret retention properties of 39 calibration compounds on a biphenylsiloxane-bonded stationary phase (Kinetex biphenyl) for acetone-water binary mobile phase systems containing 30-70% v/v. Variation in system constants, phase ratios, and retention factors of acetone-water binary mobile phases systems were compared with more commonly used acetonitrile and methanol mobile phase systems. Retention properties of acetone mobile phases on a Kinetex biphenyl column were more similar to that of acetonitrile than methanol mobile phases except with respect to selectivity equivalency. Importantly, selectivity differences arising between acetone and acetonitrile systems (the lower hydrogen-bond basicity of acetone-water mobile phases and differences in hydrogen-bond acidity, cavity formation and dispersion interactions) could be exploited in reversed-phase liquid chromatography method development on a Kinetex biphenyl stationary phase.

Unique selectivity of tetrahydrofuran-2-propanol-water ternary mobile phases on a superficially porous particle column in reversed-phase liquid chromatography.

Three mixed mobile phase organic modifiers, tetrahydrofuran: 2-propanol 1:1 (v/v), tetrahydrofuran: 2-propanol: 1:3 (v/v), and tetrahydrofuran: 2-propanol: 3:1 (v/v) were studied at 20-70% (v/v) total organic solvent compositions. The solvent strength parameters for the three mixed organic modifiers and system properties were compared to those of more established binary solvent systems, acetonitrile-water and methanol-water. To interpret intermolecular interactions responsible for retention for the three mixed mobile phase organic modifiers, system maps were constructed and compared with acetonitrile and methanol. Three mixed organic mobile phase modifiers on one stationary phase chemistry (Kinetex C18) provide different selectivity than the more established acetonitrile and methanol mobile phase modifiers on the same stationary phase (Kinetex C18) as well as different stationary phase chemistries (Kinetex Biphenyl, Kinetex Phenyl-Hexyl, Kinetex F5, Kinetex XB-C18, and Kinetex EVO C18). The solvation parameter models for all three mixed mobile phase systems the coefficient of determination ranged from 0.991 to 0.999, the Fisher statistic from 338 to 1850, and the standard error of the estimate ranged from 0.024 to 0.097.

Recent advances for estimating environmental properties for small molecules from chromatographic measurements and the solvation parameter model.

The transfer of neutral compounds between immiscible phases in chromatographic or environmental systems can be described by six solute properties (solute descriptors) using the solvation parameter model. The solute descriptors are size (McGowan's characteristic volume), V, excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity and basicity, A and B, and the gas-liquid partition constant on n-hexadecane at 298.15 K, L. V and E for liquids are accessible by calculation but the other descriptors and E for solids are determined experimentally by chromatographic, liquid-liquid partition, and solubility measurements. These solute descriptors are available for several thousand compounds in the Abraham solute descriptor databases and for several hundred compounds in the WSU experimental solute descriptor database. In the first part of this review, we highlight features important in defining each descriptor, their experimental determination, compare descriptor quality for the two organized descriptor databases, and methods for estimating Abraham solute descriptors. In the second part we focus on recent applications of the solvation parameter model to characterize environmental systems and its use for the identification of surrogate chromatographic models for estimating environmental properties.

Analytical derivatizations in environmental analysis.

Analytical derivatization is a technique that alters the structure of an analyte and produces a product more suitable for analysis. While this process can be time-consuming and add reagents to the procedure, it can also facilitate the isolation of the analyte(s), enhance analytes' stability, improve separation and sensitivity, and reduce matrix interferences. Since derivatization is a functional group analysis, it improves selectivity by separating reactive from neutral compounds during sample preparation. This technique introduces detector-orientated tags into analytes that lack suitable physicochemical properties for detection at low concentrations. Notably, many regulatory bodies, especially those in the environmental field, require these characteristics in analytical methods. This review focuses on note-worthy analytical derivatization methods employed in environmental analyses with functional groups, phenol, carboxylic acid, aldehyde, ketone, and thiol in aqueous, soil, and atmospheric sample matrices. Both advantages and disadvantages of analytical derivatization techniques are discussed. In addition, we discuss the future directions of analytical derivatization methods in environmental analysis and the potential challenges.

Analysis of the solvent strength parameter (linear solvent strength model) for isocratic separations in reversed-phase liquid chromatography.

The solvent strength parameter (slope) and intercept (log kw) of the linear solvent strength model are determined for methanol-water (17 columns), acetonitrile-water (15 columns), acetone-water (7 columns), tetrahydrofuran-water (6 columns), and 2-propanol-water (4 columns) for varied compounds. It is shown that the linear region of the plots of the retention factor (log k) against the volume fraction of organic solvent (ϕ) is largely a system property independent of solute type for compounds with accessible retention factors. Solvent strength parameters for methanol (3.12 ± 0.12), acetonitrile (2.78 ± 0.18), acetone (2.71 ± 0.11), and tetrahydrofuran (2.95 ± 0.24) are assigned for siloxane-bonded silica and porous graphitic carbon columns as an average of the compound-specific experimental values. Statistical analysis indicates that the compound-specific solvent strength parameters are column dependent and limited as a general solvent property. Evaluation of the column-specific solvent strength parameters provides further evidence that the average solvent strength parameter is column dependent. The column-specific solvent strength values are compared with the hypothetical water-organic solvent distribution systems using the system constants of the solvation parameter models as variables confirming the column dependence of the solvent strength parameter. The column-specific solvent strength parameters can be predicted by the solvation parameter model with a typical deviation of about 0.12 over a range of 1.69 to 6.33 for the experimentally determined values. The intercept of the linear solvent strength model is shown to be both column and organic solvent dependent. Compound column-specific values are adequately described by the solvation parameter model. Log kw cannot be recommended as a descriptor of solute properties since it has no clear connection to a real distribution system.

Solvation properties of acetone-water mobile phases in reversed-phase liquid chromatography.

The solvation parameter model is used for the selectivity evaluation of siloxane-bonded reversed-phase columns with mobile phases containing from 20-70 % (v/v) acetone-water. System constants determined at 10 % (v/v) increments of acetone solvent were utilized for the construction of system maps and correlation diagrams on five columns with different stationary phase chemistry; superficially porous octadecylsiloxane-bonded silica (Kinetex C18), electrostatic-shielded octadecylsiloxane-bonded silica (Luna Omega PS C18, diisobutyloctadecyl-bonded silica(Kinetex XB-C18), phenylhexyl-bonded silica (Kinetex Phenyl-Hexyl) and octylsiloxane-bonded silica (Kinetex C8). For all columns and acetone-water compositions the calibration n = 34 to 39 had a range for the coefficient of determination from 0.988 to 0.998, Fisher statistic from 277 to 1551 and a standard error of the estimate from 0.024 to 0.097. A comparison of the system constants for acetonitrile and methanol compositions for the same separation conditions confirms that the general solvation properties of acetone mobiles phases are more similar to that of acetonitrile than methanol and that method transfer should not be difficult.

Determination of physicochemical properties of ionic liquids by gas chromatography.

Over the years room temperature ionic liquids have gained attention as solvents with favorable environmental and technical features. Both chromatographic and conventional methods afford suitable tools for the study of their physicochemical properties. Use of gas chromatography compared to conventional methods for the measurement of physicochemical properties of ionic liquids have several advantages; very low sample concentrations, high accuracy, faster measurements, use of wider temperature range and the possibility to determine physicochemical properties of impure samples. Also, general purpose gas chromatography instruments are widely available in most laboratories thus alleviating the need to purchase more specific instruments for less common physiochemical measurements. Some of the main types of physicochemical properties of ionic liquids accessible using gas chromatography include gas-liquid partition constants, infinite dilution activity coefficients, partial molar quantities, solubility parameters, system constants of the solvation parameter model, thermal stability, transport properties, and catalytic and other surface properties.

Pesticide analysis in cannabis products.

Pesticide residue analysis in cannabis has become a subject of growing interest in North America since recent legalization in Canada and decriminalization for medicinal or recreational use in most US states. To meet regulatory and quality control standards, cannabis products should be tested for both authorized and unauthorized pesticides. In Canada, testing requirements mandated by Health Canada stipulate pesticide contaminant limits of quantification values of 0.02-3.0 µg/g, 0.01-2.5 µg/g and 0.01-1.5 µg/g for cannabis dried flowers, oil and fresh plants, respectively. Sample preparation and clean up methods reported in the literature for pesticide analysis in cannabis products include liquid-liquid extraction, solid-phase extraction, solid-phase microextraction and QuEChERS whereas separation and detection methods include thin-layer chromatography, capillary electrophoresis, high-performance liquid chromatography and gas chromatography in combination with various detectors such as UV and mass spectrometers. Advantages and disadvantages of the various analytical methods used in pesticide analysis of cannabis products are evaluated in this review. Furthermore, challenges ahead and future directions are discussed.

Selectivity evaluation of core-shell sislica columns for reversed-phase liquid chromatography using the solvation parameter model.

For the selectivity evaluation of core-shell silica, siloxane-bonded reversed-phase columns by the solvation parameter model a minimal set of thirty-five calibration compounds were identified for applications with mobile phases containing from 20-70 % (v/v) methanol- or acetonitrile-water. The Kennard-Stone uniform mapping algorithm was employed to select the calibration compounds from a larger database of compounds with known retention properties used previously for column selectivity evaluation. The number and identity of the calibration compounds was optimized by considering the statistical quality of the calibration models, the absolute value for the standard deviation of the individual system constants, and the closeness of the estimated system constants for the calibration models to the values for the full data set on seven core-shell columns with different morphology for mobile phases containing 50 % (v/v) methanol- or acetonitrile-water. The predictive capability of the calibration models was evaluated for an external test set for 50 % (v/v) methanol-water for the same columns with a typical root mean square error of prediction (log k) of 0.028 for the thirty-five calibration compounds (n = 35) models. For all columns and mobile phase compositions the calibration models with n = 35 had a range for the coefficient of determination from 0.999 to 0.970 with < 5 % smaller than 0.99 (84 models) and a standard error of the estimate from 0.011 to 0.057 with 75 % < 0.030. System constants determined at 10 % (v/v) increments of organic solvent were utilized for the construction of system maps and correlation diagrams on Kinetex columns with octadecylsiloxane-bonded (C18 and EVO C18), diisobutyloctadecylsiloxane-bonded (XB-C18) octylsiloxane-bonded (C8), biphenylsiloxane-bonded (Biphenyl), phenylhexylsiloxane-bonded (Phenyl-Hexyl) and pentafluorophenylpropylsiloxane-bonded (F5) silica stationary phases for 20-70 % (v/v) methanol- and acetonitrile-water mobile phases. System maps for the Kinetex Phenyl-Hexyl column and correlation diagrams for columns of similar selectivity (Kinetex C8 and Phenyl-Hexyl) and dissimilar selectivity (Kinetex EVO C18 and Biphenyl) is used to illustrate the general approach to selectivity evaluation.

Determination of physicochemical properties of small molecules by reversed-phase liquid chromatography.

The physicochemical properties of small molecules that can be determined by retention measurements in reversed-phase liquid chromatography include solvent-based properties inferred from equilibrium processes occurring predominantly in the mobile phase and sorption properties for materials which can be used as stationary phases inferred from solute-stationary phase interactions. In addition, physicochemical properties can be estimated from correlation models based on surrogate chromatographic systems with a similar capability for intermolecular interactions to the chemical or biological system. Examples of properties determined by direct methods include molecular descriptors (solvation parameter model), acid dissociation constants, formation constants, and surface properties of solids determined by inverse liquid chromatography. Examples of properties estimated by indirect methods include hydrophobicity, lipophilicity, n-octanol-water partition constant, soil-water sorption constant, non-specific toxicity to fish and microorganisms, and permeation coefficients for the blood-brain and skin-water barriers. Since all approaches depend on an accurate measurement of chromatographic retention parameters typical operational and mechanistic problems are discussed from the perspective of data quality. Fundamentally the accuracy of direct methods is limited by stationary phase heterogeneity and indirect methods by the limited number of suitable surrogate chromatographic models.

Recent advances in analytical methods for the determination of citrinin in food matrices.

Citrinin is a toxic small organic molecule produced as a secondary metabolite by fungi types Penicillium, Monascus and Aspergillus and is known to contaminate various food commodities during postharvest stages of food production. During the last 10 years, most reported methods for citrinin analysis employed enzyme-linked immunosorbent assays or high-performance liquid chromatography. Over this same time period, liquid extraction, solid-phase extraction, dispersive liquid-liquid microextraction and QuEChERS were the most cited sample preparation and clean-up methods. In this review the advantages and disadvantages of the various sample preparation, separation and detection methods for citrinin analysis over the last decade are evaluated. Furthermore, current trends, emerging technologies and the future prospects of these methods are discussed.

Models for the sorption of volatile organic compounds by diesel soot and atmospheric aerosols.

The solvation parameter model is used to characterize interactions responsible for the sorption of varied organic compounds by diesel soot and atmospheric aerosols at 15 degrees C and 50% relative humidity. Individual models are obtained for eight aerosol samples characterized as urban, suburban, rural and coastal. Combining the individual aerosol models resulted in a general aerosol model with only a minor loss of modeling power for alkanecarboxylic acids and low-molecular weight alcohols compared with the individual models. A second group of compounds identified as weak nitrogen-containing bases were consistent outliers to all models most likely due to participation in ion-exchange interactions not considered by the models. The diesel soot and atmospheric aerosols exhibit similar characteristics with respect to their sorption interactions although differences in relative magnitude allow the two particle types to be easily distinguished. Sorption interactions are favored by strong dispersion interactions for both particle types. Of note is the strong hydrogen-bond basicity and relatively weak hydrogen-bond acidity of these materials. The particles are quite dipolar/polarizable and slightly electron lone pair repulsive. The sorption properties of the atmospheric aerosols are influenced by the relative humidity, in particular, the aerosols become significantly more hydrogen-bond acidic at high relative humidity most likely due to incorporation of increasing amounts of condensed or film water in the aerosol phase. Dividing the data into training and test sets suggests that the proposed models are capable of estimating distribution constants (log K) to about 0.20 log units for diesel soot (n = 84) and 0.14 log units for the general atmospheric aerosol model (n = 385) where n indicates the number of compounds included in the model.

Solute descriptors for characterizing retention properties of open-tubular columns of different selectivity in gas chromatography at intermediate temperatures.

An iteration procedure is used to optimize the solute descriptors for 94 compounds suitable for characterizing the retention properties of open-tubular columns for gas chromatography in the intermediate temperature range of 160-240 degrees C. These solute descriptors are used to calculate the system constants of the solvation parameter model for nine open-tubular columns (SPB-Octyl, HP-5, Rtx-440, Rxi-50, Rtx-OPP, DB-1701, DB-225, HP-Innowax, and HP-88) at increments of 20 degrees C from 160 to 240 degrees C. The optimized descriptors afford a two- to three-fold improvement in the fit to the retention model compared with literature values as determined by the standard deviation of the difference between the model predicted and experimental retention factors (log k). Combining literature values for the system constants at lower temperatures (60-140 degrees C) with those obtained here allowed system maps to be constructed for the nine columns over the full temperature range of 60-240 degrees C. For a wide temperature range the system maps indicate that the relationship between the system constants and temperature is non-linear and that polar interactions are likely to be important in relative and absolute terms to quite high temperatures.

Selectivity equivalence of two poly(methylphenylsiloxane) open-tubular columns prepared with different deactivation techniques for gas chromatography.

The solvation parameter model is used to characterize the retention properties of a poly(methylphenylsiloxane) column Rxi-50 over the temperature range 60-240 degrees C. The smooth variation of the system constants with temperature affords a general picture of how the relative importance of the different intermolecular interactions change with temperature. The system constants and retention factors for varied compounds are compared with those for Rtx-50 prepared with a similar stationary phase but using a different surface deactivation technique. The two columns are shown to be nearly selectivity equivalent. The Rtx-50 column is slightly more cohesive, dipolar/polarizable and hydrogen-bond basic than Rxi-50, while Rxi-50 is slightly more electron lone pair attractive and hydrogen-bond acidic. Only the difference in hydrogen-bond acidity can be identified with some certainty as related to the difference in deactivation processes. For compounds with a separation greater than 0.2 retention factor units on Rtx-50, it should be relatively straightforward to achieve an acceptable separation for the same compounds on Rxi-50.

Estimation of descriptors for hydrogen-bonding compounds from chromatographic and liquid-liquid partition measurements.

Retention factors obtained by gas chromatography and reversed-phase liquid chromatography on varied columns and partition constants in different liquid-liquid partition systems are used to estimate WSU descriptor values for 36 anilines and N-heterocyclic compounds, 13 amides and related compounds, and 45 phenols and alcohols. These compounds are suitable for use as calibration compounds to characterize separation systems covering the descriptor space E=0.2-3, S=0.4-2.1, A=0-1.5, B=0.1-1.5, L=2.5-10.0 and V=0.5-2.2. Hydrogen-bonding properties are discussed in terms of structure, the possibility of induction effects, intramolecular hydrogen bonding and steric factors for anilines, amides, phenols and alcohols. The relationship between these parameters and observed descriptor values are difficult to predict from structure but facilitate improving the general occupancy of the descriptor space by creating incremental changes in hydrogen-bonding properties. It is verified that the compounds included in this study can be merged with an existing database of compounds recommended for characterizing separation systems.

System maps for retention of small neutral compounds on a superficially porous particle column in reversed-phase liquid chromatography.

The system constants of the solvation parameter model are used to prepare system maps for the retention of small neutral molecules on the ocadecylsiloxane-bonded silica superficially porous particle stationary phase (Kinetex C18) for aqueous-organic solvent mobile phases containing 10-70% (v/v) methanol or acetonitrile. A comparison of the system constants with eight commercially available octadecylsiloxane-bonded silica columns for the same separation conditions confirms that the general retention properties of Kinetex C-18 are similar to totally porous octadecylsiloxane-bonded silica stationary phases and that method transfer should be no more difficult than that usually observed when substituting one octadecylsiloxane-bonded silica column for another.

System maps for retention of small neutral compounds on a biphenylsiloxane-bonded silica stationary phase in reversed-phase liquid chromatography.

The system constants of the solvation parameter model are used to prepare system maps for the retention of small neutral compounds on a biphenylsiloxane-bonded superficially porous silica stationary phase (Kinetex Biphenyl) for aqueous-organic solvent mobile phases containing 10-70% (v/v) methanol or acetonitrile. The retention properties of the biphenylsiloxane-bonded phase are shown to be complementary to an octadecylsiloxane-bonded silica (Kinetex C-18) and a pentafluorophenylpropylsiloxane-bonded silica stationary phases (Discovery HS F5). The retention properties of the Kinetex Biphenyl column are similar to an ether-linked phenylpropylsiloxane-bonded silica phase (Synergi Polar RP) with only small differences in relative retention.