Conventional Sample Preparation Procedures Research Articles

Dispersant-First Dispersive Liquid-Liquid Microextraction (DF-DLLME), a Novel Sample Preparation Procedure for NDMA Determination in Metformin Products

Since December 2019, global batch recalls of metformin pharmaceutical products have highlighted an urgent need to control N-nitrosodimethylamine (NDMA) contamination to demonstrate patient safety and maintain supply of this essential medicine. Due to their formulation, the metformin extended-release products present difficult analytical challenges for conventional sample preparation procedures, such as artefactual (in-situ) NDMA formation, gelling, and precipitation. To overcome these challenges, a new version of dispersive liquid-liquid microextraction (DLLME) termed dispersant-first DLLME (DF-DLLME) was developed and optimized for the analysis of NDMA in metformin extended-release products using a detailed Design of Experiments (DoE) to optimize sample preparation. Gas chromatography-high resolution accurate mass-mass spectrometry (GC-HRAM-MS) combined with automated DF-DLLME were successfully applied to monitor the NDMA levels of two different metformin extended-release AstraZeneca products to ultra-trace levels (parts per billion). The additional benefits associated with DF-DLLME, which include automation, time/costs saving, and greener sample preparation, make this novel technique easier to transfer from a development to Quality Control (QC) environment. In addition, this also offers an attractive candidate for the wider platform analysis of N-nitrosamines in pharmaceutical drug products.

Recent advances and trends in miniaturized sample preparation techniques.

Advances in the area of sample preparation are significant and have been growing significantly in recent years. This initial step of the analysis is essential and must be carried out properly, consisting of a complicated procedure with multiple stages. Consequently, it corresponds to a potential source of errors and will determine, at the end of the process, either a satisfactory result or a fail. One of the advances in this field includes the miniaturization of extraction techniques based on the conventional sample preparation procedures such as liquid-liquid extraction and solid-phase extraction. These modern techniques have gained prominence in the face of traditional methods since they minimize the consumption of organic solvents and the sample volume. As another feature, it is possible to reuse the sorbents, and its coupling to chromatographic systems might be automated. The review will emphasize the main techniques based on liquid-phase microextraction, as well as those based upon the use of sorbents. The first group includes currently popular techniques such as single drop microextraction, hollow fiber liquid-phase microextraction, and dispersive liquid-liquid microextraction. In the second group, solid-phase microextraction techniques such as in-tube solid-phase microextraction, stir bar sorptive extraction, dispersive solid-phase extraction, dispersive micro solid-phase microextraction, and microextraction by packed sorbent are highlighted. These approaches, in common, aim the determination of analytes at low concentrations in complex matrices. This article describes some characteristics, recent advances, and trends on miniaturized sample preparation techniques, as well as their current applications in food, environmental, and bioanalysis fields.

High-reliability zircon separation for hunting the oldest material on Earth: An automatic zircon separator with image-processing/microtweezers-manipulating system and double-step dating

Despite the recent development in radiometric dating of numerous zircons by LA-ICPMS, mineral separation still remains a major obstacle, particularly in the search for the oldest material on Earth. To improve the efficiency in zircon separation by an order of magnitude, we have designed/developed a new machine – an automatic zircon separator (AZS). This is designed particularly for automatic pick-up of 100 μm-sized zircon grains out of a heavy mineral fraction after conventional separation procedures. The AZS operates in three modes: (1) image processing to choose targeted individual zircon grains out of all heavy minerals spread on a tray, (2) automatic capturing of the individual zircon grains with micro-tweezers, and (3) placing them one-by-one in a coordinated alignment on a receiving tray. The automatic capturing was designed/created for continuous mineral selecting without human presence for many hours. This software also enables the registration of each separated zircon grain for dating, by recording digital photo-image, optical (color) indices, and coordinates on a receiving tray. We developed two new approaches for the dating; i.e. (1) direct dating of zircons selected by LA-ICPMS without conventional resin-mounting/polishing, (2) high speed U-Pb dating, combined with conventional sample preparation procedures using the new equipment with multiple-ion counting detectors (LA-MIC-ICPMS). With the first approach, Pb-Pb ages obtained from the surface of a mineral were crosschecked with the interior of the same grain after resin-mounting/polishing. With the second approach, the amount of time required for dating one zircon grain is ca. 20 s, and a sample throughput of >150 grains per hour can be achieved with sufficient precision (ca. 0.5%).We tested the practical efficiency of the AZS, by analyzing an Archean Jack Hills conglomerate in Western Australia with the known oldest (>4.3 Ga) zircon on Earth. Preliminary results are positive; we were able to obtain more than 194 zircons that are over 4.0 Ga out of ca. 3800 checked grains, and 9 grains were over 4300 Ma with the oldest at 4371 ± 7 Ma. This separation system by AZS, combined with the new approaches, guarantees much higher yield in the hunt for old zircons.

Electric field-assisted solid phase extraction and cleanup of ionic compounds in complex food matrices: Fluoroquinolones in eggs

The use of electric fields as additional driving forces in sample preparation techniques is an innovative approach that is environmentally friendly, straightforward, and able to overcome several limitations of conventional sample preparation procedures. In this work, the advantages of electric field-assisted solid phase extraction (E-SPE) using syringe-type cartridges were demonstrated for the extraction of four fluoroquinolones (FQs) in their anionic forms. The FQs were extracted from eggs and subsequently determined by UHPLC–MS/MS. The use of electric fields during the washing and final elution steps resulted in a significant improvement of the extraction efficiencies for almost all FQs when compared to conventional SPE. Intra- and inter-day assays showed coefficients of variation below 10%. The better cleanup also resulted in the appearance of less precipitated matter in the final eluate, as well as reduced matrix effects. The results showed that the electrophoretic forces derived from electric fields are a promising way of significantly increasing the extraction efficiency of ionic analytes, while minimizing matrix effects associated with complex samples.

Mechanistic Evaluation of Matrix Effect on Three Different Model of Mass Spectrometer by Using a Model Drug

In this research work we have tried to emphasis that the synergistic approach is required wherein during method development sample processing and instrument i.e., mass spectrometershall be evaluated in synchronized manner to get the best possible combination of processing technique and instrument model to get a method with no or minimal matrix effect. To perform this research work polar molecule niacin is considered as a model drug to evaluate the synergistic approach. Plasma was treated with three different conventional sample preparation procedures (PPT, LLE and SPE) and samples processed with the three methodology were then analyzed on three different instrument models of AB Sciex i.e., API-3000, API-3200, API-4000. Except for type of sample processing technique and instrument model, rest of the parameters like aliquot volume, internal standard working solution volume and chromatographic conditions were kept constant to avoid contribution of these factors due to these variables. Samples were analyzed using Inertsil® CN-3 as an analytical column and mobile phase consist of acetonitrile - solution-1(0.002% formic acid in water, v/v) in the ratio of 70:30, v/v. Result evidently showed that matrix effect was minimized through SPE technique over LLE technique and behavior of the co-elute matrix also changed significantly with ion-source design of the mass spectrometer. Consequently, the development result clearly showed that matrix effect was nullified by samples prepared by SPE technique and analyzed on API-3000. Results obtained from API- 3000 and API-4000 models were also comparable in terms of matrix effect. API-3000 in combination with solid phase extraction procedure was selected to further validate the method as API-4000 showed charge competition of internal standard. Overall, the results indicate that extraction procedure plays a crucial role to control matrix effect but to get the best result LC have to be coupled with mass spectrometer with proper ion source.

Automated on-line liquid–liquid extraction system for temporal mass spectrometric analysis of dynamic samples

Most real samples cannot directly be infused to mass spectrometers because they could contaminate delicate parts of ion source and guides, or cause ion suppression. Conventional sample preparation procedures limit temporal resolution of analysis. We have developed an automated liquid–liquid extraction system that enables unsupervised repetitive treatment of dynamic samples and instantaneous analysis by mass spectrometry (MS). It incorporates inexpensive open-source microcontroller boards (Arduino and Netduino) to guide the extraction and analysis process. Duration of every extraction cycle is 17 min. The system enables monitoring of dynamic processes over many hours. The extracts are automatically transferred to the ion source incorporating a Venturi pump. Operation of the device has been characterized (repeatability, RSD = 15%, n = 20; concentration range for ibuprofen, 0.053–2.000 mM; LOD for ibuprofen, ∼0.005 mM; including extraction and detection). To exemplify its usefulness in real-world applications, we implemented this device in chemical profiling of pharmaceutical formulation dissolution process. Temporal dissolution profiles of commercial ibuprofen and acetaminophen tablets were recorded during 10 h. The extraction-MS datasets were fitted with exponential functions to characterize the rates of release of the main and auxiliary ingredients (e.g. ibuprofen, k = 0.43 ± 0.01 h−1). The electronic control unit of this system interacts with the operator via touch screen, internet, voice, and short text messages sent to the mobile phone, which is helpful when launching long-term (e.g. overnight) measurements. Due to these interactive features, the platform brings the concept of the Internet-of-Things (IoT) to the chemistry laboratory environment.

Why liquid membrane extraction is an attractive alternative in sample preparation

Abstract The use of liquid membrane-based extractions is increasingly seen as offering an alternative to conventional sample preparation procedures in analysis of chemical species in both environmental and biological media. In this article, emphasis is placed on the attractiveness of liquid membrane-based extraction techniques to a variety of analytical applications such as speciation of metal ions in biological fluids, time-weighted average field sampling, and time-weighted average passive field sampling. Further, the area of designing new and much simpler miniaturized configurations, which is enjoying much attention in liquid membrane-based extraction techniques, is discussed.

In Situ Delineation Etch Reveals Subtle Detail in SEM Images of Ion Milled Cross Sections Enabling In-Fab 3-D Metrology and Characterization

Abstract Control of layer thickness is critically important in the manufacture of semiconductor devices. Cross-sectioning exposes device structures for direct examination but conventional sample preparation procedures are difficult, time consuming, and grossly destructive. Cross sections created by focused ion beam (FIB) milling are easier, faster, and less destructive but have not offered the clear layer delineation provided by etching in the conventional sample preparation process. A new gas etch capability (Delineation Etch™ from FEI Company) offers results that are equivalent to conventional wet-etch preparations in a fraction of the time from a single, automated system in the fab without destroying the wafer. The new etch process also has application in milling high-aspect-ratio holes to create contacts to buried metal layers, and in deprocessing devices to reveal silicon and polysilicon structures.

Evaluation of screening procedures for bioconcentratable organic chemicals in effluents and sediments

AbstractScreening procedures have been developed by the U.S. Environmental Protection Agency (EPA) to isolate and tentatively identify nonpolar organic chemicals in effluent and sediment samples with high potential to form chemical residues in aquatic organisms. The objective of this study was to determine if the sample components tentatively identified by the effluent‐and sediment‐screening procedures actually form chemical residues in aquatic organisms. This evaluation consisted of analyzing effluent and sediment samples from a field site with discharges from two coke‐manufacturing facilities using the screening procedures. Effluent, sediment, crayfish (Decapoda), and sunfish (Lepomis sp.) samples from the field site were also prepared using conventional sample preparation procedures and analyzed for the tentatively identified chemicals (TIDs) reported by the screening procedures. Results of the screening procedures were then compared to the results of the analyses on the samples prepared using the conventional sample preparation procedures. For the effluent‐screening procedure, 182 of 183 TIDs in Coke Plant 1 effluent and all of the 7 TIDs in Coke Plant 2 effluent were found in the crayfish, sunfish, and/or sediment samples downstream of the discharges. For the sediment‐screening procedure, 92 of 93 TIDs and all of 47 TIDs in sediment samples from two sampling stations downstream of the discharges were found in the crayfish and/or sunfish samples.

EVALUATION OF SCREENING PROCEDURES FOR BIOCONCENTRATABLE ORGANIC CHEMICALS IN EFFLUENTS AND SEDIMENTS

Screening procedures have been developed by the U.S. Environmental Protection Agency (EPA) to isolate and tentatively identify nonpolar organic chemicals in effluent and sediment samples with high potential to form chemical residues in aquatic organisms. The objective of this study was to determine if the sample components tentatively identified by the effluent-and sediment-screening procedures actually form chemical residues in aquatic organisms. This evaluation consisted of analyzing effluent and sediment samples from a field site with discharges from two coke-manufacturing facilities using the screening procedures. Effluent, sediment, crayfish (Decapoda), and sunfish (Lepomis sp.) samples from the field site were also prepared using conventional sample preparation procedures and analyzed for the tentatively identified chemicals (TIDs) reported by the screening procedures. Results of the screening procedures were then compared to the results of the analyses on the samples prepared using the conventional sample preparation procedures. For the effluent-screening procedure, 182 of 183 TIDs in Coke Plant 1 effluent and all of the 7 TIDs in Coke Plant 2 effluent were found in the crayfish, sunfish, and/or sediment samples downstream of the discharges. For the sediment-screening procedure, 92 of 93 TIDs and all of 47 TIDs in sediment samples from two sampling stations downstream of the discharges were found in the crayfish and/or sunfish samples.

Quantitative polymer additive analysis by multidimensional chromatography using on‐line coupled microcolumn size exclusion chromatography as a preliminary separation

AbstractThe quantitative determination of polymer additives using a multidimensional system consisting of microcolumn size exclusion chromatography (micro SEC) coupled on‐line to a capillary gas chromatograph and to a conventional size LC system is described. The results obtained were compared to conventional sample preparation procedures consisting of dissolution of the polymer followed by precipitation and analysis of the supernatant. Results obtained for two polymer systems studied indicated losses for some additives using the precipitation approach.An on‐line coupled micro‐SEC‐LC system was investigated for the separation of compounds in which the volatility may not allow determination via capillary GC. The lower volumetric dispersion given by the microcolumns allowed introduction of the complete additive fraction without detrimental effects on the peak shape or resolution.

Quantitative Analysis of Carbon-14 Labelled Polychlorinated Biphenyls and Hexachlorobenzene in Biological Samples Using an Oxidative Combustion Method

Abstract Carbon-14 labelled glucose, polychlorinated biphenyls, and hexachlorobenzene at concentrations of 0.01-1200 nanograms were oxidized in a combustion chamber at 900C. The 14CO2 emitted was trapped in an organic base. and its radioactivity measured. Recovery rates of 95-104% were obtained from samples oxidized with mannitol, while recoveries of samples oxidized with dried fish ranged from 93—101%. This method provides an alternate technique of sample preparation for materials that may yield a highly quenched solution following conventional sample preparation procedures for liquid scintillation measurements.