Application of silver nanoparticles and principal component-artificial neural network models for simultaneous determination of levodopa and benserazide hydrochloride by a kinetic spectrophotometric method

A multicomponent analysis method based on principal component analysis-artificial neural network model (PC-ANN) is proposed for the simultaneous determination of levodopa (LD) and benserazide hydrochloride (BH). The method is based on the reaction of levodopa and benserazide hydrochloride with silver nitrate as an oxidizing agent in the presence of PVP and formation of silver nanoparticles. The reaction monitored at analytical wavelength 440 nm related to surface plasmon resonance band of silver nanoparticles. Differences in the kinetic behavior of the levodopa and benserazide hydrochloride were exploited by using principal component analysis, an artificial neural network (PC-ANN) to resolve concentration of analytes in their mixture. After reducing the number of kinetic data using principal component analysis, an artificial neural network consisting of three layers of nodes was trained by applying a back-propagation learning rule. The optimized ANN allows the simultaneous determination of analytes in mixtures with relative standard errors of prediction in the region of 4.5 and 6.3 for levodopa and benserazide hydrochloride respectively. The results show that this method is an efficient method for prediction of these analytes.     

Simultaneous determination of rifampicin and isoniazid by continuous-flow chemiluminescence with artificial neural network calibration

In this paper a continuous-flow chemiluminescence (CL) system with artificial neural network calibration is proposed for simultaneous determination of rifampicin and isoniazid. This method is based on the different kinetic spectra of the analytes in their CL reaction with alkaline N-bromosuccinimide as oxidant. The CL intensity was measured and recorded every second from 1 to 300 s. The data obtained were processed chemometrically by use of an artificial neural network. The experimental calibration set was 20 sample solutions. The relative standard errors of prediction for both analytes were approximately 5%. The proposed method was successfully applied to the simultaneous determination of rifampicin and isoniazid in a combined pharmaceutical formulation.     

Enantioselective determination of chloroquine and its n-dealkylated metabolites in plasma using liquid-phase microextraction and LC-MS

A selective method using three-phase liquid-phase microextraction (LPME) in conjunction with LC-MS-MS was devised for the enantioselective determination of chloroquine and its n-dealkylated metabolites in plasma samples. After alkalinization of the samples, the analytes were extracted into n-octanol immobilized in the pores of a polypropylene hollow fiber membrane and back extracted into the acidic acceptor phase (0.1 M TFA) filled into the lumen of the hollow fiber. Following LPME, the analytes were resolved on a Chirobiotic V column using methanol/ACN/glacial acetic acid/diethylamine (90:10:0.5:0.5 by volume) as the mobile phase. The MS detection was carried out using multiple reaction monitoring with ESI in the positive ion mode. The optimized LPME method yielded extraction recoveries ranging from 28 to 66%. The method was linear over 5-500 ng/mL and precision (RSD) and accuracy (relative error) values were below 15% for all analytes. The developed method was applied to the determination of the analytes in rat plasma samples after oral administration of the racemic drug.     

Stereoselective determination of hydroxychloroquine and its metabolites in human urine by liquid-phase microextraction and CE

Liquid-phase microextraction based on polypropylene hollow fibers and CE were applied for the chiral determination of hydroxychloroquine (HCQ) and its metabolites (desethylchloroquine, DCQ; desethylhydroxychloroquine, DHCQ; bisdesethylchloroquine, BDCQ) in human urine. The analytes were extracted from 3 mL of urine spiked with the internal standard (metoprolol) and alkalinized with 250 muL of 2 M NaOH. The analytes were extracted into 1-octanol impregnated in the pores of the hollow fiber, and into an acid acceptor solution inside the hollow fiber. The electrophoretic separations were carried out in 100 mmol/L Tris buffer (pH adjusted to 9.0 with phosphoric acid) containing 1% w/v S-beta-CD and 30 mg/mL HP-beta-CD with a constant voltage of +18 kV. The method was linear over the concentration range of 10-1000 ng/mL for each HCQ stereoisomer and 21-333 ng/mL for each metabolite stereoisomer. Within-day and between-day assay precision and accuracy for the analytes were studied at three concentration levels for each stereoisomer and were lower than 15%. The developed method was applied for the determination of the cumulative urinary excretion of HCQ, DCQ, and DHCQ after oral administration of rac-HCQ to a health volunteer. The results obtained are in agreement with previous literature data.     

Synchronous fluorimetric determination of salicylic acid and diflunisal in human serum using partial least-squares calibration

The simultaneous determination of salicylic acid and diflunisal in human serum has been accomplished by synchronous fluorimetry, in combination with partial least-squares multivariate calibration. The total luminescence information of the analytes has been used to optimize the spectral data set for the calibration, by analysis of the three-dimensional excitation-emission matrices. The synchronous spectrum, maintaining a constant difference of Deltalambda = 128 nm between the emission and excitation wavelengths, has been selected as optimum to perform the determination. The method is based on the fluorescence of these compounds in chloroform containing 1% (v/v) acetic acid. Serum samples are treated with trichloroacetic acid to remove the proteins, and both analytes are extracted into chloroform-1% (v/v) acetic acid prior to the determination. For concentrations ranging from 60-240 mug ml(-1) of each drug, analytical recoveries range from 96% to 103% for salicylic acid and from 97% to 105% for diflunisal.     

Rapid and selective determination of UV filters in seawater by liquid chromatography-tandem mass spectrometry combined with stir bar sorptive extraction

Fast liquid chromatography coupled to triple-quadrupole tandem mass spectrometry was employed for the determination of six UV filters in seawater. The separation of the analytes was achieved in less than 5 min; polarity switching was used as four of the analytes were ionized in positive mode and the remaining two in negative mode. Two ionization sources were employed and compared: atmospheric pressure chemical ionization (APCI) gave better results than electrospray ionization (ESI) for all analytes, with higher reproducibility and lower detection limits. Therefore APCI was chosen for the determination of the analytes in seawater samples using stir bar sorptive extraction-liquid desorption (SBSE-LD).Quantitative analysis was performed in multiple reaction monitoring (MRM) mode; fragmentation pathways of the analytes with regard to the formation of the MRM ions were also proposed.For the analysis of seawater samples, calibration curves were drawn using SBSE in spiked seawater. All figures of merit of the method were satisfactory; limits of detection were particularly low for the four analytes ionized in positive mode, being in the range 8-31 ng/L. The method was applied to the determination of the six UV filters in seawater samples from Liguria, Italy. Only benzophenone-3 (BP-3) and ethylhexyl methoxycinnamate (EHMC) were measured in the analyzed samples; some of the remaining analytes were also detected but always below the limit of quantitation.     

Partial least-squares with residual bilinearization for the spectrofluorimetric determination of pesticides. A solution of the problems of inner-filter effects and matrix interferents

This paper demonstrates for the first time the power of a chemometric second-order algorithm for predicting, in a simple way and using spectrofluorimetric data, the concentration of analytes in the presence of both the inner-filter effect and unsuspected species. The simultaneous determination of the systemic fungicides carbendazim and thiabendazole was achieved and employed for the discussion of the scopes of the applied second-order chemometric tools: parallel factor analysis (PARAFAC) and partial least-squares with residual bilinearization (PLS/RBL). The chemometric study was performed using fluorescence excitation-emission matrices obtained after the extraction of the analytes over a C18-membrane surface. The ability of PLS/RBL to recognize and overcome the significant changes produced by thiabendazole in both the excitation and emission spectra of carbendazim is demonstrated. The high performance of the selected PLS/RBL method was established with the determination of both pesticides in artificial and real samples.     

Simultaneous determination of metformin and glimepride in pharmaceutical dosage form by reverse-phase liquid chromatography

A simple, rapid, and precise reversed-phase liquid chromatographic method has been developed for the simultaneous determination of metformin in combination with glimepride. Under the developed conditions, good separation of the analytes was achieved in short analysis time. Several parameters affecting the separation of the analytes were studied, including pH and the concentration of SDS. The method is validated and shown to be linear in the range of 25 microg/mL to 150 microg/mL for metformin and 0.1 microg/mL to 0.6 microg/mL for glimepride. The method is applied for the analysis of these analytes in commercially available tablets.     

Spectrofluorimetric flow injection method for the individual and successive determination of L-cysteine and L-cystine in pharmaceutical and urine samples.

A flow injection configuration is proposed for the determination of L-cysteine and L-cystine individually and for mixtures of both analytes. The procedure is based on the rapid oxidation of L-cysteine by thallium(III) with concomitant formation of fluorescent thallium(I). The inclusion of a selecting valve and of a copper-coated cadmium column in the configuration allows the successive determination of two analytes. Linear calibration graphs were obtained between 5 x 10(-6) and 5 x 10(-5) mol dm-3 of L-cysteine and between 2 x 10(-6) and 2 x 10(-5) mol dm-3 of L-cystine. The applicability of the method to the determination of L-cysteine and L-cystine in pharmaceutical preparations was demonstrated by investigating the effect of potential interferents and by the analysis of commercial preparations. The method was successfully applied to the determination of L-cysteine and L-cystine in urine samples.     

Computer aided exploitation of mathematical models of processes. A general description of the approach

An approach is described which helps the experimenter in: (a) selecting the most appropriate method of determination of physicochemical or technical parameters, (b) optimization of analytical procedures or of determination of physicochemical parameters, (c) indication of the possible improvements of the experimental technique applied, (d) diagnosis of the model and the data handling scheme applied in the determination of parameters, and other. The examples presented are based on simulated experiments. They concern selection of the best method for determination of an equilibrium constant and for determination of two analytes from a single instrumental (photometric, potentiometric) titration curve.     

Development of multiple monolithic fiber solid‐phase microextraction and liquid chromatography–tandem mass spectrometry method for the sensitive monitoring of aminoglycosides in honey and milk samples

A simple and sensitive method for the simultaneous extraction and determination of six aminoglycosides in honey and milk samples was developed using multiple monolithic fiber solid‐phase microextraction and liquid chromatography with tandem mass spectrometry. The multiple monolithic fibers based on poly(methacrylic acid‐co‐ethylenedimethacrylate) monolith as the extraction medium was used to concentrate target analytes. Because there were abundant carboxyl groups in the monolith, the monolithic fibers could extract aminoglycosides effectively through cation‐exchange and hydrophobic interactions. To obtain optimum extraction performance, several extraction parameters including desorption solvent, adsorption and desorption time, pH value and ionic strength in sample matrix, were investigated in detail. Under the optimized extraction conditions, the limits of detection of the proposed method were 0.10–0.30 and 0.23–0.59 μg/kg for honey and milk samples, respectively. Satisfactory linearity was achieved for analytes with the coefficients of determination above 0.99. At the same time, the developed method showed acceptable method repeatability and reproducibility. Finally, the proposed method was successfully applied to the determination of aminoglycosides in real honey and milk samples. Recoveries obtained for the determination of six target analytes in spiking samples ranged from 67.9 to 110%, and the relative standard deviations were in the range of 1.2–11%.     

A chemometric study of the simultaneous determination of calcium and magnesium in natural waters

A method for the simultaneous spectrophotometric determination of calcium and magnesium in mineral waters with an FIA system is tested. The method is based on the reaction between the analytes and arsenazo(III) at pH 8.5. The calculations of the amounts of both analytes in the samples are carried out with the H-point standard addition method (HPSAM) for ternary mixtures, and with a partial least squares (PLS) model after a proper variable selection. The results obtained for the determination of calcium were comparable using both methods. The employment of the HPSAM brings to our attention the influence of the calcium concentration in the sample to the development of the reaction between magnesium and arsenazo(III). HPSAM also permits to estimate the concentration of magnesium in the samples.     

Differential pulse polarographic determination of arsenic, selenium and tellurium at mug levels

An analytical method, based on differential pulse polarography, for determination of arsenic, selenium and tellurium in solid matrices, is described. The method involves decomposition of the matrix with a mixture of nitric, perchloric and hydrofluoric acid, isolation of tellurium from the other analytes by liquid-liquid extraction (from 4M hydrochloric acid with methyl isobutyl ketone), and determination of the analytes. Tellurium is determined separately, and arsenic is determined in the same solution as selenium after determination and oxidation of the selenium and addition of catechol. Graphitized carbon black and chelating resin were used to eliminate the organic solvent in the aqueous solution and avoid interferences due to the other metals of the matrix. The decomposition, the influence of each analyte on the determination of the others, and the extraction process were given particular attention. The method is characterized by>96% recovery, with a relative standard deviation ranging from 2 to 10% at ppm levels.     

Separation and determination of B vitamins and essential amino acids in health drinks by CE-LIF with simultaneous derivatization

An efficient and sensitive method for the separation and determination of three essential amino acids and three B vitamins by CE-LIF with a simultaneous derivatization procedure was developed. The conditions for derivatization and separation of these micronutrients were investigated. FITC was used as the reagent for fluorescence tagging of arginine (Arg), valine (Val), tryptophan (Trp), folic acid (FA), and niacinamide (NA). Riboflavin (RF) was detected without derivatization. Derivatization of analytes dissolved in borate solution was performed by successive introduction of fluorescence reagent and analytes followed by water bathing at 43°C. The molar ratio of sample/reagent (S/R), derivatization temperature, and incubation time significantly influenced the efficiency of derivatization. To maximize the fluorescence yield, a high S/R (≥20) was required. The nonderivatized RF and five derivatized analytes were separated in the optimized CE-LIF system with the application of 22 kV voltage and 25 mM borate buffer at pH 9.85. Validation of the method showed good linearity for the corrected peak areas versus standard concentrations for the six analytes. The RSDs (n = 3) of the migration time and the peak area obtained for the analytes ranged from 0.4 to 1.1% and from 1.9 to 4.4%, respectively. The developed method, with the lowest LOD of 0.5 nM, was successfully applied for the efficient derivatization and determination of B vitamins in four health drink samples.     

Simultaneous quantitation of the highly lipophilic atovaquone and hydrophilic strong basic proguanil and its metabolites using a new mixed-mode SPE approach and steep-gradient LC

A bioanalytical method is described for the simultaneous quantitative analysis of the highly lipophilic atovaquone and the strong basic proguanil with metabolites in plasma. The drugs are extracted from protein precipitated plasma samples on a novel mixed-mode solid-phase extraction (SPE) column containing carboxypropyl and octyl silica as functional groups. The analytes are further separated and quantitated using a steep-gradient liquid chromatographic method on a Zorbax SB-CN column with UV detection at 245 nm. Two different internal standards (IS) are used in the method to compensate for both types of analytes. A structurally similar IS to atovaquone is added with acetonitrile to precipitate proteins from plasma. A structurally similar IS to proguanil and its metabolites is added with phosphate buffer before samples are loaded onto the SPE columns. A single elution step is sufficient to elute all analytes. The method is validated according to published guidelines and shows excellent performance. The within-day precisions, expressed as relative standard deviation, are lower than 5% for all analytes at three tested concentrations within the calibration range. The between-day precisions are lower than 13% for all analytes at the same tested concentrations. The limit of quantitation is 25 nM for the basic substances and 50 nM for atovaquone. Several considerations regarding development and optimization of a method for determination of analytes with such a difference in physiochemical properties are discussed.     

Miniaturized matrix solid-phase dispersion and solid-phase clear-up combined with capillary electrophoresis for efficient determination of trace bioactive components in complicated sample matrix: Take Wubi Shanyao Pill as an example

Accurate quantitative analysis of trace analytes in a complicated matrix is a challenge in modern analytical chemistry. An appropriate analytical method is considered to be one of the most common gaps during the whole process. In this study, a green and efficient strategy based on miniaturized matrix solid-phase dispersion and solid-phase extraction combined with capillary electrophoresis was first proposed for extracting, purifying and determining target analytes from complicated matrix, using Wubi Shanyao Pill as an example. In detail, 60 mg of samples were dispersed on MCM-48 to obtain high yields of analytes, then the extract was purified with a solid-phase extraction cartridge. Finally, four analytes in the purified sample solution were determined by capillary electrophoresis. The parameters affecting the extraction efficiency of matrix solid-phase dispersion, purification efficiency of solid-phase extraction and separation effect of capillary electrophoresis were investigated. Under the optimized conditions, all analytes demonstrated satisfactory linearity (R²>0.9983). What's more, the superior green potential of the developed method for the determination of complex samples was confirmed by the Analytical GREEnness Metric Approach. The established method was successfully applied in the accurate determination of target analytes in Wubi Shanyao Pill and thus provided reliable, sensitive, and efficient strategy support for its quality control.     

Calibration of titration methods

Summary A calibration method is proposed which makes it possible to use titration techniques in the presence of systematic errors, even if these errors depend on the concentrations of the analytes. The approach uses an empirical calibration model which approximates the relationship between apparent (found) and true concentrations of the analytes. Also a calibration of the physical model of the titration process is proposed, as well as a method of determination of the model parameters, which are useful when analytes are determined by fitting the model to experimental data of titration. Both approaches, empirical and based on the physical model, may be applied jointly. The example presented reveals high efficiency of the proposed approach in cases when a deficient physicochemical model of the titration process is used in the determination of an analyte concentration (simulated titration data applied). The calibration proposed may be considered as a generalization of the titrant standardization used in the conventional volumetric analysis. It may be applied to all titration techniques and for all methods of end-point detection and determination of the concentration of analytes. It opens new possibilities for the development of titration methods. Permanent address: Department of Analytical Chemistry, Jagiellonian University, Karasia 3, PL-30-060 Krakow, Poland     

Determination of phosphorus and arsenic in trichlorosilane by electrothermal vaporization-inductively coupled plasma mass spectrometry with prior concentration by cuprous chloride

A method for the determination of trace impurities of phosphorus and arsenic in trichlorosilane with prior separation followed by electrothermal vaporization inductively coupled plasma mass spectrometry (ETV-ICP-MS) has been developed. The preconcentration of the analytes from the sample matrix was made by adding cuprous chloride to a 10 mL trichlorosilane sample for the formation of non-volatile compounds with the elements of interest. Upon evaporation of trichlorosilane, the analytes retained in the residue were then determined in the presence of copper as modifier by ETV-ICP-MS. The dual role of cuprous chloride both in the preconcentration and instrumental determination was investigated and discussed. By meticulous control of experimental conditions, limits of detection for these two elements as low as sub-ng/g can be achieved. The method was applied to the determination of phosphorus and arsenic in a commercially available trichlorosilane sample.     

Accurate and sensitive determination of selected hormones,endocrine disruptors,and pesticides by gas chromatography–mass spectrometry after the multivariate optimization of switchable solvent liquid‐phase microextraction

Switchable solvent liquid‐phase microextraction was combined with gas chromatography and mass spectrometry to improve the sensitivity and accuracy for the determination of selected endocrine disruptors, pesticides, and hormones. The extraction method was used to complement gas chromatography with mass spectrometry by preconcentrating analytes for trace determinations. A Box–Behnken experimental design was used to evaluate the main variables and their interaction effects, and optimum parameters were selected based on the model of experimented results. Application of optimum extraction conditions to mixed standard solutions yielded limits of detection and quantitation values between 0.20–13 and 0.90–46 ng/mL, respectively. The accuracy and the applicability of the developed method was checked in tap water and two different wastewater samples by spiked recovery tests. The percent recoveries recorded for the analytes were between 91 and 110%, and percent relative standard deviation values were all below 10%. The results indicate that the method can be used for the accurate and sensitive determination of these analytes in the presented matrixes.     

Elimination of matrix effect and simultaneous determination of multi-components in complex systems by matrix coefficient non-linearity multivariate calibration based on single point response signals.

In order to deal with the matrix effect in the simultaneous determination of multi-components in a complex system, we have developed a novel method named matrix coefficient multivariate calibration method (MCMCM) for simultaneously determining n analytes in complex systems. The calibration models of n analytes, which are based on the experimental data of known samples, are first transformed into n linear equations, and then the equations are solved to obtain matrix calibration coefficients of the analytes in congeneric samples. In this way, the concentrations of n analytes in the unknown sample could be obtained easily and simultaneously by solving another n-variate linear equations with the help of the matrix calibration coefficients obtained-above. The method proposed in this work has been tested by voltammetry and atomic absorption spectrometry (AAS) with satisfactory results. On determining the elements such as Cu, Pb, Cd, Ni, Zn, Fe, Mn, Co, Ca, Mg, etc. in synthetic samples, the relative standard deviations (RSDs) of the results were 0.91 - 4.5%, and the recoveries were 95.8 - 105%. For actual samples, the RSDs and the recoveries were 1.5 - 6.9 and 92.0 - 110%, respectively.