Low LOQ Research Articles

Development, optimization and comparison of solid-liquid and liquid-liquid microextraction for the determination of four flavonols in Schinus molle L. using high-performance liquid chromatography coupled with second-order data modeling.

Flavonoids are particularly interesting because they have a broad spectrum of biological effects, including antioxidant and free radical scavenging activities. In this work, solid-liquid microextraction and dispersive liquid-liquid microextraction enhanced by ultrasound were developed and compared with the conventional method (Soxhlet extraction) to optimize the extraction of four flavonoids: rutin, quercitrin, quercetin, and myricetin in samples of Schinus molle (Aguaribay). During the development of the analytical method, different chemometric tools were used to optimize the microextraction procedure. In addition, an analytical method based on high-performance liquid chromatography with diode array detector (HPLC-DAD) and secondorder calibration using multivariate curve resolution-alternating least square (MCR-ALS) is presented to quantify the flavonoids with limits of quantification between 0.011 and 0.082µgmL-1. Finally, solid-liquid microextraction using 4.00mL water/ethanol (54.3:45.7%), 14s vortex, and 45min was selected as the most suitable method due to its high recovery rate and environmental friendliness (with a greenness score of 0.78). After the optimization step, the concentrations found in the plant samples were 1825.3, 632.6, 110.2, and 18.9µgg-1 for rutin, quercitrin, quercetin, and myricetin, respectively. The present work is the first achievement of simultaneously determining these four analytes with exceptional sensitivity, demonstrating lower LOQs compared to previous reports.

Analytical quality-by-design guided development of a novel and robust HPTLC method for quantifying plumbagin from Plumbago species

The study utilizes an analytical quality-by-design (AQbD) approach to establish a robust and efficient HPTLC method for plumbagin quantification in plumbago species. The highest-risk critical method parameters (CMP; concentration of plumbago and composition of mobile phase) and most appropriate critical analytical attributes (CAA; Peak area and retention factor [Rf]) were employed in the AQbD methodology. These CMP were tuned for higher plumbagin recovery using the central composite design (CCD) experiment. The created approach was validated by the requirements outlined in the International Conference on Harmonization (ICH) Q2 (R2). Every plate involved in the proposed method validation has been subjected to the passing requirements of the system suitability test (SST). The low LOD (16.93 ng/mL) and LOQ (49.68 ng/mL) values and the minimal divergence in intra- and inter-day studies validate the developed method’s high precision and sensitivity. Further experiments employing the proposed method to determine the amount of plumbagin from the two distinct plant sources harvested under two different climate conditions determined the highest plumbagin content in P. indica, which is in line with the results. To summarize, the AQbD method may be used in other plant systems to optimize various factors and get a greater concentration of the desired plant metabolite.

Multi-sample analytical workflow for the determination of isoprostanes in oral fluid: A new tool for non-invasive evaluation of oxidative stress.

Oxidative stress is a pathological condition that contributes to the onset of various diseases. In this way, studying oxidative stress could lead to significant discoveries in the field of therapeutic and preventive medicine. Lipid peroxidation is the most significant event in the oxidative stress process and the gold standard biomarkers for endogenous oxidative damage to lipids are isoprostanes (IsoPs). This project aims to develop a reliable analytical method for the liquid-liquid microextraction technique, parallel artificial liquid membrane extraction (PALME) and LC-MS/MS analysis. PALME allowed to obtain a significant enrichment factor and, at the same time, a good sample purification by removing compounds that cause signal suppression, thereby reducing matrix effect. The chromatographic and mass spectrometric conditions have been fine tuned to improve the sensitivity of the method and therefore obtaining very low LOD and LOQ values. The recovery values obtained for the analytes are slightly above 50%, except for 6-keto Prostaglandin F1A (24%). Matrix effects were ≤ -10 %, with LODs ranging between 1 and 5pgmL-1. The developed method is characterized by high sensitivity and low consumption of organic solvents, according to the principles of Green Analytical Chemistry and enables the determination of basal levels of IsoPs in oral fluid by processing 96 samples simultaneously.

Development and validation of a UV spectrophotometric method for simultaneous estimation of teneligliptin hydrobromide hydrate and pioglitazone hydrochloride in pharmaceutical dosage form

BackgroundThis study presents the development and validation of a UV spectrophotometric method for the simultaneous estimation of teneligliptin hydrobromide hydrate (TEN) and pioglitazone hydrochloride (PIO) in pharmaceutical dosage forms. The method measures absorbance at 243 nm for TEN and 265 nm for PIO. Validation was conducted according to ICH guidelines, covering specificity, linearity, range, precision, accuracy, limit of detection, limit of quantification, and robustness.ResultsThe method exhibited linearity in the 2–25 µg/ml concentration range for both TEN and PIO, with correlation coefficients close to 1. Precision studies showed low % RSD values, indicating excellent repeatability and minimal intra- and inter-day variability. Accuracy was confirmed through recovery studies, with results within the 98–102% range. The method demonstrated sensitivity with low LOD and LOQ values. Robustness testing showed stability and consistency under varying conditions. Analysis of tablet formulations confirmed the accurate quantification of both drugs.ConclusionThe developed UV spectrophotometric method offers a simple, sensitive, and cost-effective solution for the simultaneous estimation of TEN and PIO in pharmaceutical formulations. It is suitable for routine analysis and quality assessment of tablet dosage forms.

Evaluation of selenocysteine contents in Se-enriched yogurt by Utilizing online post column derivative − High-Performance liquid chromatography

This study demonstrated a novel method using online post-column derivatization high-performance liquid chromatography (PCD-HPLC) to evaluate selenocysteine (SeC) in Se-enriched yogurt. The liquid chromatography process utilized a C18 column. The mobile phase A was composed of 4.0 mM borate buffer adjusted to pH 5.0, while mobile phase B was a 50:50 (v/v) mixture of methanol and acetonitrile. The mobile phases were combined at a ratio of 70:30, with a flow rate of 1 mL min−1. SeC was derivatized to bis-Fmoc selenocystine after separation, using a PCD solution (0.03 mM Fmoc, pH 10, 20 mM borate buffer, and 1.0 mL min−1 flow rate) and detected with a photodiode array detector (DAD) for sensitivity enhancement. The method exhibited excellent linearity (0.023 to 0.20 mg L-1, r2 = 0.9996), with a low LOD and LOQ of 0.018 mg L-1 and of 0.040 mg L-1, respectively. Repeatability and reproducibility were satisfactory, with recoveries of 95.50 % ± 1.49 % (the proposed PCD-HPLC) and 94.33 % ± 0.44 % (sample preparation). This method effectively analyzed the conversion of selenite ions (SeO32-) to SeC by lactic acid bacteria in yogurt, highlighting Se-enriched yogurt as a valuable dietary source of SeC. However, the synthesis efficiency of SeC decreased at inorganic Se supplementation levels above 1.0 mg Se L-1, potentially leading to the formation of less toxic elemental Se (Se0). Therefore, the proposed online PCD-HPLC method proves reliable for SeC analysis in Se-enriched yogurt, providing insights into Se speciation and optimizing Se enrichment processes.

An absolute quantification method for selected MFGM proteins in infant formula using targeted proteomics

Milk fat globule membrane (MFGM) proteins are receiving increased attention due to their reported benefits for human health, particularly in infant populations. Challenges exist in MFGM protein quantification due to their low quantities, complex chemistry, interactions with other matrix components, and the high matrix complexity. In this study, a subset of four MFGM proteins were selected as relevant targets for identification and quantification in an infant formula (IF) matrix: butyrophilin, mucin 1, xanthine dehydrogenase/oxidase, and perilipin 2. An analytical protocol for absolute quantification of these four MFGM proteins in IF was successfully developed and validated. Additionally, the feasibility to apply the method in selected MFGM ingredients was also demonstrated. The method demonstrated good performance; high accuracy and robustness, low LOQ and uncertainty, while controlling the matrix effect. This study represents a report of an analytical method to quantify selected MFGM proteins in IF.

Determination and health risk assessment of carbamate pesticide residues in date palm fruits (Phoenix dactylifera) using QuEChERS method and UHPLC-MS/MS

This study aimed to investigate carbamate pesticide residues in different varieties of date palm fruits in the UAE, utilizing UHPLC-MS/MS. For sample preparation and clean-up, the efficiency and performance of different QuEChERS dispersive solid-phase extraction kits were compared. Precision and recovery were assessed at 10 μg kg−1 for the three kits, revealing that Kit 2 demonstrated the best performance. The selected QuEChERS method was validated to detect 14 carbamate residues in 55 date samples. The method exhibited strong linearity with R2 > 0.999 and low LOD (0.01–0.005 μg kg−1) and LOQ (0.003–0.04 μg kg−1). Excellent accuracy (recovery: 88–106%) and precision (RSD: 1–11%) were observed, with negligible matrix effect (− 4.98–13.26%). All samples contained at least one carbamate residue. While most detected residues were below their MRLs, carbosulfan was found in 21 samples, propoxur in 2 samples, and carbofuran in 1 sample above their MRLs. The hazard index (HI) was calculated for carbosulfan, phenmedipham, carbaryl, propoxur, carbofuran, and methomyl to assess potential health risks for date consumers. All HI values were below the safety limit of 1.0, indicating that the consumption of dates does not pose a non-carcinogenic health risk for adults and children.

Hybrid Quadrupole Mass Filter - Radial Ejection Linear Ion Trap and Intelligent Data Acquisition Enable Highly Multiplex Targeted Proteomics.

Targeted mass spectrometry (MS) methods are powerful tools for selective and sensitive analysis of peptides identified by global discovery experiments. Selected reaction monitoring (SRM) is currently the most widely accepted MS method in the clinic, due to its reliability and analytical performance. However, due to limited throughput and the difficulty in setting up and analyzing large scale assays, SRM and parallel reaction monitoring (PRM) are typically used only for very refined assays of on the order of 100 targets or less. Here we introduce a new MS platform with a quadrupole mass filter, collision cell, linear ion trap architecture that has increased acquisition rates compared to the analogous hardware found in the Orbitrap™ Tribrid™ series instruments. The platform can target more analytes than existing SRM and PRM instruments - in the range of 5000 to 8000 peptides per hour. This capability for high multiplexing is enabled by acquisition rates of 70-100 Hz for peptide applications, and the incorporation of real-time chromatogram alignment that adjusts for retention time drift and enables narrow time scheduled acquisition windows. Finally, we describe a Skyline external software tool that implements the building of targeted methods based on data independent acquisition chromatogram libraries or unscheduled analysis of heavy labeled standards. We show that the platform delivers ~10x lower LOQs than traditional SRM analysis for a highly multiplex assay and also demonstrate how analytical figures of merit change while varying method duration with a constant number of analytes, or by keeping a constant time duration while varying the number of analytes.

Aptamer-functionalized Fe3O4/MWCNTs@Mo-CDs nanozyme for rapid colorimetric detection toward Escherichia coli

The pathogenic bacteria induced foodborne disease has been detrimental to public health worldwide. Herein, the peroxidase (POD)-like Fe3O4/MWCNTs@Mo-CDs (FMMC) nanozyme was applied for the detection of Escherichia coli (E. coli). The E. coli aptamer was conjugated with the surface of the FMMC, which effectively enhanced the POD-like activity attributing to the higher affinity to the substrate, and then specific capture of E. coli in food matrices, leading to the reduction of POD-like activity. Therefore, a robust and facile colorimetric aptasensor was developed for detecting E. coli with a wide linear range of 101–106 CFU/mL, low LOQ of 101 CFU/mL and LOD of 0.978 CFU/mL. The aptasensor demonstrated the satisfied selectivity for E. coli compared to the other strains. This method possessed the potential application for fast in situ screening of foodborne pathogens in food products.

LC-MS analysis of polar and highly polar organic pollutants in Barcelona urban groundwater using orthogonal LC separation modes.

Groundwater samples may contain thousands of organic pollutants from infiltration of surface water, sewer leakages, and to a minor extent from public water supply network losses. Polar (0 < log D < - 2.0) and very polar substances (log D < - 2.0) have been largely beyond the scope of applied analytical methodologies in environmental monitoring because of challenges related to their extraction from the sample and subsequent chromatographic separation. In this study, we developed an analytical workflow for 96 pollutants covering a broad polarity range, including pharmaceuticals, industrial chemicals, and artificial sweeteners, potentially seeping through the soil in urban areas. The Besos aquifer located at the Northern-eastern edge of the city of Barcelona was chosen as a study area due to the deterioration of the quality of the aquifers over the past years and the proven presence of numerous pollutants. The methodology consisted of vacuum-assisted evaporation (VAE) followed by chromatographic separation of the sample on two columns with orthogonal retention mechanisms, namely, an HSS T3 column (modified C18) and a BEH amide column (HILIC). The analytes were detected by high-resolution mass spectrometry on a Q Exactive Orbitrap system in data-independent acquisition mode. Taking into consideration the retention as well as the peak shape, a Quality Score (QS) was assigned for each analyte to evaluate the quality of each chromatographic peak of each compound. While 67 compounds, including 19 polar and 48 moderately polar, were satisfactorily retained on an HSS T3, 29 compounds, including 14 highly polar, 14 polar, and one moderately polar, were analyzed in the BEH amide column. The optimized methodology was applied for the analysis of 89 out of 96 validated contaminants with satisfactory recoveries in samples collected from seven wells, providing low LODs (0.02 to 0.45ng L-1) and LOQs (0.06 to 1.34ng L-1). A number of highly polar and polar compounds not previously reported to occur in GW, including artificial sweeteners, pharmaceuticals, and industrial chemicals, were detected at concentrations as high as few g L-1.

Quantification of Etoricoxib in Low Plasma Volume by UPLC-PDA and Application to Preclinical Pharmacokinetic Study.

An ultra-performance liquid chromatography with photodiode array (UPLC-PDA) UV detection method was developed here for the first time for simple, rapid, selective and sensitive quantification of the commonly prescribed selective cyclooxygenase-2 (COX-2) inhibitor etoricoxib in low plasma volumes (50 μL). The method includes protein precipitation followed by liquid-liquid extraction, evaporation and reconstitution. A gradient mobile phase of 75:25 going to 55:45 (v/v) water:acetonitrile (1 mL/min flow rate) was applied. Total run time was 8 min, representing a significant improvement relative to previous reports. Excellent linearity (r2 = 1) was obtained over a wide (0.1-12 µg/mL) etoricoxib concentration range. Short retention times for etoricoxib (4.9 min) and the internal standard trazodone (6.4 min), as well as high stability, recovery, accuracy, precision and reproducibility, and low etoricoxib LOD (20 ng/mL) and LOQ (100 ng/mL), were achieved. Finally, the method was successfully applied to a pharmacokinetic study (single 20 mg/kg orally administered etoricoxib mini-capsule) in rats. In conclusion, the advantages demonstrated in this work make this analytical method both time- and cost-efficient for drug monitoring in pre-clinical/clinical settings.

Desitometric Development and Validation for Simultaneous Determination of Antiretroviral Drugs Lamivudine, Zidovudine and Nevirapine in Fixed-Dose Combination Tablets

A cutting-edge high-performance thin layer chromatography (HPTLC) approach designed for simultaneous measurement of tablets containing drugs like lamivudine, nevirapine, and zidovudine. Chromatograms were performed employing chloroform and methanol (8:2 v/v) on pre-coated silica gel aluminum thin-layer chromatography (TLC) plates. The data was quantified using the optical density absorbance mode at 271 nm. The Rf values for lamivudine, zidovudine, and nevirapine were 0.140, 0.523, and 0.678, respectively. Linearity was found for lamivudine, zidovudine and nevirapine at concentrations of 150 to 900 ng band-1, 300 to 1800 and 200 to 1200 ng band-1, respectively. Lamivudine had a lower limit of detection (LLoD) of 27.36 ng band-1 and a lower limit of quantitation (LLoQ) of 82.91 ng band-1, whereas zidovudine had LoQs of 64.13 ng band-1 and 194.34 ng band-1. For nevirapine, the values were 35.52 and 107.64 ng band-1, respectively. Lamivudine had a lower LoD of 27.36 ng band-1 and a lower LoQ of 82.91 ng band-1, whereas zidovudine had LoQs of 64.13 and 194.34 ng band-1. For nevirapine, the values were 35.52 and 107.64 ng band-1, respectively. The recovery, specificity, and accuracy of this device have been demonstrated. This new formulation evaluated market tablet formulations of the above drugs (Duovir, Cipla Ltd.). The developed method demonstrated the ability to simultaneously identify these drugs from quantitative data without interference.

Evaluation of Iron Chlorin e6 disappearance and hydrolysis in soil and garlic using salting-out assisted liquid-liquid extraction coupled with high-performance liquid chromatography and ultraviolet-visible detection

Iron Chlorin e6 (ICE6), a star plant growth regulator (PGR) with independent intellectual property rights in China, has demonstrated its efficacy through numerous field experiments. We innovatively employed salting-out assisted liquid-liquid extraction (SALLE) with HPLC-UV/Vis to detect ICE6 residues in water, soil, garlic seeds, and sprouts. Using methanol and a C18 column with acetonitrile: 0.1% phosphoric acid mobile phase (55:45, v:v), we achieved a low LOQ of 0.43 to 0.77 μg kg−1. Calibration curves showed strong linearity (R2 > 0.992) within 0.01 to 5.00 mg kg−1. Inter-day and intra-day recoveries (0.05 to 0.50 mg kg−1) demonstrated high sensitivity and accuracy (recoveries: 75.36% to 107.86%; RSD: 1.03% to 8.78%). Additionally, density functional theory (DFT) analysis aligned UV/Vis spectra and indicated ICE6's first-order degradation (2.03 to 4.94 days) under various environmental conditions, mainly driven by abiotic degradation. This study enhances understanding of ICE6's environmental behavior, aids in risk assessment, and guides responsible use in agroecosystems.

One-pot synthesis of novel chitosan-salicylaldehyde polymer composites for ammonia sensing

Chitosan (Chs)-salicylaldehyde (Sal) polymer derivatives were formed via the reaction of Chs-Sal with zinc oxide nanoparticles (ZnO NPs) and beta-cyclodextrin (β-CD). These polymers were synthesized through inclusion with β-CD and doping with ZnO NPs to give pseudopolyrotaxane and Chs-Sal/ZnO NPs composite, respectively, for low-temperature detection and sensing of NH3 vapors as great significance in environmental control and human health. Additionally, the polymer (Chs-Sal/β-CD/ZnO NPs) was prepared via the insertion of generated composite (Chs-Sal/ZnO NPs) through β-cyclodextrin ring. The structural and morphological characterizations of the synthesized derivatives were confirmed by utilizing FTIR, XRD and, SEM, respectively. Also, the optical properties and thermal gravimetric analysis (TGA) of the synthesized polymers were explored. The obtained results confirmed that using β-CD or ZnO NPs for modification of polymer (Chs-Sal) dramatically enhanced thermal stability and optical features of the synthesized polymers. Investigations on the NH3-sensing properties of Chs-Sal/β-CD/ZnO NPs composite were carried out at concentrations down to 10 ppm and good response and recovery times (650 s and 350 s, respectively) at room temperature (RT) and indicated that modification by β-CD and doping with ZnO NPs effectively improves the NH3-sensing response of Chs-Sal from 712 to 6192 using Chs-Sal/β-CD/ZnO NPs, respectively, with low LOD and LOQ of 0.12 and 0.4 ppb, respectively.

Uporedno spektrofotometrijsko određivanje 3-hidroksiflavona bazirano na kompleksima cinka i aluminijuma i njihovi antioksidatni profili

Flavonoids, as plant-derived compounds, were essential active components in traditional medicine for centuries. Their potential or confirmed effects include antiviral, antimutagenic, antiinflammatory, antibacterial, vasodilatory, and anticancer properties. The promotion of a plantbased diet, along with the benefits of consuming flavonoids, has recently become increasingly attractive. 3-Hydroxyflavone (3HF) is the structural spine of flavonols, an important subgroup of flavonoids. Although 3HF itself does not exist in plants per se, it exerts many of its effects because of its characteristics that allow it to prevent free radical generation. This work is focused on the characterization of 3HF complexes with zinc(II) and aluminium(III) ions (Zn-3HF and Al-3HF, respectively). Besides this, a simple, fast, and low-priced spectrophotometric method for 3HF determination, with very low LOD and LOQ, based on Zn-3HF and Al-3HF formation, was established. A slight advantage is given to the modification with Al3+ ion on pH 4.91, due to very low LOD and LOQ values of 1.83×10-7 molL-1 , and 5.50×10-7 molL-1 , respectively, and a high correlation coefficient, R =0.99986. Furthermore, the antioxidant ability of Zn-3HF, Al-3HF, and parent 3HF was examined by the ABTS and DPPH tests. They brought the Zn-3HF complex to the fore as a potential antioxidative agent.

Quantification of inorganic anions in surface and drinking waters using ion chromatography

The Republic of Bulgaria regulates the quality of surface waters for drinking and domestic purposes, monitoring anions like F-, Cl-, Br-, I-, BrO3-, NO2-, NO3-, SO42-, PO43-, and SCN-. The presence of NO3- and NO2- in water is undesirable, as they have a harmful effect on human health. It is also well known that CN- as opposed to SCN- has acute toxic and lethal effects on living organisms including humans. In the present study, an instrumental method was developed and optimized for the separation and quantification of inorganic anions in surface and drinking water using ion chromatography. The analytical characteristics of the proposed instrumental method were determined. The oxidation of CN- to OCN- was investigated, and the optimal experimental conditions for the oxidation were established. The achieved low LOD and LOQ of the analyzed inorganic anions allows their detection and quantification in surface and drinking waters. The applicability of the proposed chromatographic method was determined in the analysis of surface and bottled waters. The analyzed anions in bottled waters were close to the label's values, only one spring water showed significant deviations.

Development and validation of a green RP-HPLC method for detection and quantitation of meropenem trihydrate in the bulk: A comparison with HPTLC method

This research introduces an eco-friendly green Reverse-Phase High Performance Liquid Chromatography (RP-HPLC) method for detecting and quantifying meropenem trihydrate. Traditional methods use buffered solutions, gradient mobile phases, and longer retention times, but this method offers a rapid RP-HPLC technique with a C8 column and isocratic mobile phase (60% methanol, 40% ultra-pure water), eliminating the need for buffers and acetonitrile. It features a short 2.1-minute retention time and a high r² value of 0.9995. It delivers accuracy (101.1-102.3%) and precision (RSD ≤ 2%), coupled with low LOD and LOQ values of 1.72 and 5.20 µg/ml. Aqueous dilution simplifies sample preparation, reducing degradation and interference. The method is compared with an HPTLC method, showing an extended linear range (6.25-200 µg/ml for HPLC, 7.81-62.5 µg/ml for TLC) and high sensitivity, making it significant for meropenem trihydrate quality control in bulk and dosage forms.

2 in 1 versus 1 plus 1 – Outcomes of the transformation of adsorptive stripping method for the Ni2+ and Co2+ determination

AbstractDue to the similar chemical properties of Ni2+ and Co2+, several dozens of adsorptive stripping voltammetric (AdSV) methods have been developed for their simultaneous determination. The question was would there be some benefits if a stripping method made for simultaneous determination of Ni2+ and Co2+ will be optimized for the determination of only one of them (Ni2+). It was found that the optimized method has for an order of magnitude lower LOQ (1.89×10−10 M), an order of magnitude lower influence of Co2+, and the applicability of one calibration line for four orders of magnitude of Ni2+ concentration. The influence of some common anions and cations has been examined. The developed method was successfully applied for nickel content determination in real samples. The suitability of the developed method for the determination of Co2+ from the same solution in the second run, upon optimizations of deposition potential and time, was also explored. The LOQ obtained for Co2+ (3.61×10−11 M) is almost two orders of magnitude lower than LOQ of the method for simultaneous determination of both cations and, its LOD and LOQ are among few lowest obtained by AdSV methods for Co2+ determination. The developed method for Ni2+ and Co2+ determination from the same solution in two successive runs has significantly better analytical performances than the starting method for their simultaneous determination in one run.

Nanomaterial-based magnetic surface molecularly imprinted polymers for specific extraction and efficient recognition of dibutyl phthalate.

A rapid and selective sorbent for the enrichment of dibutyl phthalate (DBP) from water and Chinese Baijiu samples was established using magnetic surface molecularly imprinted polymers (MSMIPs) combined with gas chromatography-mass spectrometer (GC-MS). The MSMIPs were synthesized using a magnetic nanosphere material with silica layer, increasing the polymer surface area as a carrier. Compared with the traditional methods, the addition of magnetic microspheres simplified the process of food substrate purification and significantly shortened the pre-concentration time. The MSMIPs adsorption conforms to the Freundlich isotherm model as multilayer adsorption on an inhomogeneous surface and the pseudo-second-order model. The developed MSMIPs combined with GC-MS method showed good linearity in DBP concentration range of 0.02-1.0mg L-1 with low LOD (0.0054mg L-1) and LOQ (0.018mg L-1), and obtained good recoveries in real samples (95.2-97.2%) with RSD<5.0% (n=9), which were consistent with those from Chinese national standard method.

Investigations on the electrochemical behavior of sunitinib and metabolites N-desethyl-sunitinib and sunitinib-N-oxide and its selective determination using molecularly imprinted polymer-based sensor

Sunitinib (SUN) is an orally administered tyrosine kinase inhibitor and is mainly metabolized via N-deethylation to form the primary active metabolite N-desethyl-sunitinib (M1) and via oxidation to sunitinib-N-oxide (M2). In this study, we first investigated the electrochemical behavior of sunitinib and its N-desethyl and N-oxide metabolites on a bare glassy carbon electrode (GCE) by cyclic voltammetry (CV) technique. Based on the results, a plausible electrooxidation mechanism is proposed, yielding the oxo-desfluoro-sunitinib (quinoneimine metabolite) via oxidative defluorination of sunitinib. After this phase of the study, due to the low sensitivity and selectivity results obtained from the bare GCE, we aimed to develop the first molecularly imprinted polymer (MIP)-based electrochemical sensor for the sensitive and selective determination of SUN. The MA@SDS/MIP-GCE sensor was prepared by thermal polymerization of methacrylic acid (MA) as a functional monomer in the presence of SUN on a GCE surface under the optimized parameters such as template/monomer ratio, drop amount, polymerization temperature and time, removal solution and time, and rebinding time, which affect the structure and response of the sensor. The surface characterization of the developed sensor was performed by scanning electron microscopy (SEM), and the electrochemical characterization was performed by CV and electrochemical impedance spectroscopy (EIS). The electroanalytical performance of the MA@SDS/MIP-GCE sensor was tested by differential pulse voltammetry (DPV) under the optimized conditions in comparison with the NIP-based sensor. The linearity of the developed sensor for the determination of SUN was investigated in the concentration range of 0.5 – 5.0 nM for standard and serum solutions with low LOD and LOQ values. The application of the MIP sensor for the determination of SUN in pharmaceutical dosage form (capsule) and serum samples was demonstrated with excellent recoveries. The results showed that the MA@SDS/MIP-GCE sensor is a sensitive, specific, selective, rapid, and economical option for the quantitative determination of SUN.