Evaluation of various liquid chromatography-quadrupole-linear ion trap-mass spectrometry operation modes applied to the analysis of organic pollutants in wastewaters

The LC-MS/MS analysis of a group of 14 organic pollutants in wastewater – including pharmaceuticals (analgesics/anti-inflammatories, lipid regulators and diuretics), pesticides (diuron) and disinfectants (chlorophene) – has been carried out using a hybrid triple quadrupole-linear ion trap-mass spectrometer (QqLIT). In order to take advantage of the capabilities of the QqLIT system, two methods have been developed and compared, based on the application of different operation modes. One of them uses selected reaction monitoring (SRM), which is the standard mode for quantitative LC-MS/MS analysis. The other is based on the use of an information dependent acquisition scan function (IDA), which allows the combination of a SRM acting as the survey scan and an enhanced product ion scan (EPI) as dependent scan within the same analysis. Performance of both methods was compared, especially in terms of their limits of detection and identification capability. The advantages and limitations of both techniques are discussed. Finally, the two methodologies developed were applied to real samples for evaluation of effluent wastewater in a treatment plant on the south-eastern Mediterranean coast of Spain. The presence of most of the target compounds was detected at mean concentrations ranging from 50 ng/L (mefenamic acid) to 3373 ng/L (hydrochlorothiazide).     

Ultraviolet Photolysis and Ortho-Phthalaldehyde-Mercaptoethanol Derivatization of Pharmaceuticals for Enhanced Fluorescence Detection in HPLC

Abstract

Several classes of nitrogenous pharmaceutical were examined for fluorescence after ultraviolet (UV) radiation induced photolysis followed by reaction with o-phthalaldehyde-2-mercaptoethanol (OPA-MERC), and after UV photolysis alone. Photolyses were examined in water, mixtures of methanol/water (1:1), and acetonitrile/water (1:1). Acetone was assessed as a photosensitizer to enhance photolysis and fluorescence response. Flow injection analysis and high-performance liquid chromatographic techniques were used for several pharmaceuticals. The analytes were subjected to UV photolysis and reaction with OPA-MERC reagent for generation of fluorophores that responded to fluorescence detection. During photolysis, solvent type as well as the presence of photosensitizers seem to play a significant role in the formation of primary amines and fluorophores. Photochemical transformation products of some of the pharmaceutical chemicals are proposed. Analytical figures of merit were determined for some analytes. This fluorescence detection approach is applicable for a number of pharmaceuticals at nanogram level.     

Optimization of the Temperature for the Extraction of Pharmaceuticals from Wastewater by a Hollow Fiber Silicone Membrane

The influence of temperature on the extraction and selectivity of naproxen, ibuprofen, and triclosan by a thin-walled hollow fiber silicone rubber membrane was investigated. Determination of the diffusion coefficients and flux values at 25, 40, and 60 degrees Celsius was undertaken. The diffusion coefficient and flux were found to increase with temperature. It was also observed that at higher temperatures, mass transfer was influenced by the amount extracted in the acceptor phase. However, diffusion from the bulk donor phase through the hollow fiber silicone rubber membrane was shown to control the transport of analytes at lower temperatures. When applied to wastewater, the hollow fiber silicone rubber showed remarkable selectivity toward the analytes. However, at high temperatures, the amount of matrix components extracted also increased slightly. The amount extracted nearly doubled when extraction was performed at 40 degrees Celsius compared to 25 degrees Celsius, indicating that temperature increased the efficiency of the hollow fiber silicone rubber membrane. The application of the technique to municipal wastewater showed remarkable selectivity and reproducibility. The concentrations of these compounds were from 18.4 (1.37 percent) micrograms per liter for triclosan to 1.1 (0.16 percent) micrograms per liter for naproxen in the influent and 2.7 (0.29 percent) micrograms per liter for triclosan to 0.4 (0.01 percent) micrograms per liter for naproxen in the effluent.     

Sensitive ergotamine determination in pharmaceuticals and biological samples using cloud point preconcentration and spectrofluorimetric detection

A new cloud point extraction (CPE) method for ergotamine analysis using fluorimetric detection is described. Ergotamine from an aqueous solution was preconcentrated into a smaller surfactant-rich phase using nonionic surfactant polyoxyethylene(7.5)nonylphenylether (PONPE 7.5). Differently from the conventional CPE procedure in which the resulting surfactant-rich phase is diluted by a fluidificant before its analysis, in this method the fluorescence measurements were carried out directly onto the undiluted surfactant-rich phase. The high viscosity provided by the undiluted surfactant rich phase greatly improved the fluorescence emission of ergotamine, leading to a total enhancement factor of 1325. This spectral advantage plus the preconcentration factor achieved, contributed to the method sensitivity allowing the ergotamine determination at trace level concentration. Under optimal experimental conditions, a linear calibration curve was obtained from 3.81 × 10⁻⁷ to 1.10 μg mL⁻¹, with detection and quantification limits of 0.11 and 0.38 pg mL⁻¹, respectively. The accuracy and versatility of the present methodology were proved by analyzing ergotamine in real samples of different natures such as pharmaceuticals, urine and saliva.     

‘In situ’ preparation of nitrous acid solutions by photoreduction in a flow assembly for analysis of pharmaceuticals

The solutions of nitrite ion, or nitrous acid, are frequently used as reagent in different analytical procedures and in pharmaceutical analysis. The low stability of the aqueous solutions of this reagent implies the tedious work of freshly prepared solutions every day and being kept in the refrigerator. In this paper, a photoreactor formed by a low pressure mercury lamp and nesting in a continuous-flow manifold is studied, tested, and proposed for the in situ reduction of nitrate solution into nitrite. The conversion into nitrite is reproducible and it has been successfully applied to determination of different drugs, mostly from the sulphonamide family, in an FIA assembly.     

Atmospheric oxidative catalyst-free cross-dehydrogenative coupling of aldehydes with N-hydroxyimides

Cross-dehydrogenative coupling (CDC) reactions of aldehydes with N-hydroxyimidates such as N-hydroxysuccinimide (NHSI), N-hydroxyphthalimide (NHPI) under catalyst-free conditions is described. Moreover, the desired products can be obtained simply by recrystallization from ethanol. This method is also applicable to the synthesis of amides in excellent yields. A radical mechanism of the type shown in Scheme 4 is proposed based upon the inhibition of the reaction in the presence of TEMPO.     

Porous monolithic materials for extraction and preconcentration of pollutants from environmental waters

This review presents the strengths and weaknesses of monolithic materials for the enrichment of inorganic and organic contaminants in environmental waters. We describe the most common materials (silica, organic, and hybrid organic silica) and strategies for constructing monoliths in different moulds and shapes (tubes, cartridges, stir bars, fibers) published since 2015. The functionalization of the pore surfaces enhances their affinity towards different classes of pollutants. For instance, the incorporation of chelating groups enables the enrichment of potentially toxic metals and semi-metals in aquatic environments before the analyses by spectrometric techniques. Monolithic materials for extracting emerging pollutants, diverse classes of herbicides, and fungicides were proposed recently. Incorporation of carbon-based and magnetic nanoparticles, metal-organic frameworks, and ionic liquids enhanced their adsorption capacity by either increasing the surface area or providing multiple retention mechanisms. Monoliths with molecular recognition properties for highly selective extractions have been synthesized, including boronic functionalities and molecularly imprinted cavities. The final part describes the hybrid organic silica monoliths, emphasizing metal ions and speciation analysis hyphenated with ICP-MS. In the outlook section, we point to some fields we believe monoliths will benefit, such as their 3-D technologies preparation. We also pointed their potential applicability in portable chromatographic systems, restricted access materials, and enhanced use to preconcentrate viruses from aquatic environments.     

Determination of thermodynamic pKa values of pharmaceuticals from five different groups using capillary electrophoresis

A determination of the thermodynamic acid dissociation constants (pK_a) of 22 frequently used pharmaceuticals using capillary electrophoresis in aqueous media is presented in this work. The investigated pharmaceuticals belong to different pharmacological groups: macrolides, fluoroquinolones, sulfonamides, β‐lactams, tetracyclines, and other miscellaneous pharmaceuticals. The electrophoretic mobilities of the investigated analytes were monitored in a pH range from 2.00 to 10.82. The data were fitted with an appropriate mathematical model using a nonlinear regression analysis to obtain pK_a values. Experimentally obtained data were well described by the mathematical model chosen for each analyte that was confirmed by r² values higher than 0.99 for most of the investigated analytes. Extrapolations to zero ionic strength were used to determine the thermodynamic pK_a values. Experimentally obtained acid dissociation constants were interpreted using structural formulae of investigated analytes and the moieties corresponding to specific pK_a were identified.     

UPLC-MS/MS screening method for simultaneous identification and characterisation of acidic and basic pharmaceuticals

ABSTRACT

A new screening method was developed for the simultaneous determination of seven acidic and basic pharmaceuticals by the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) utilising triple quadrupole mass spectrometry as a detector. The target pharmaceutical compounds of interest in this work belong to different classes of pharmaceutical group with different physico-chemical properties. Both the positive and negative ionisation modes (dual ionisation mode) in electrospray ionisation (ESI) were used simultaneously. Unlike previous studies, the performance of the dual ionisation mode was compared with the positive and negative ionisation modes individually in terms of analysis time and sensitivity. Results indicate that the developed screening method was successfully applied for the simultaneous determination of the acidic and basic pharmaceutical compounds. Using dual ionisation mode reduced the analyses time while still maintaining sensitivity and quality of the analytical result. The new method was implemented in detecting the targeted analyte in a real sample of wastewater. The instrument detection limit (IDL) was as low as 9.7 fg, indicating a high sensitivity as compared to the corresponding methods. The precision of the instrument was calculated as the relative standard deviation (RSD) ranging from 1.4 to 11.0%. The limit of quantification (LOQ) for the method was over the range 0.77–177 ng L^?1 and 1.05–100 ng L^?1 for the influent and effluent wastewater, respectively.