Chromatographic fingerprinting through chemometric techniques for herbal slimming pills: A way of adulterant identification.

In the current study, gas chromatography-mass spectrometry (GC-MS) fingerprinting of herbal slimming pills assisted by chemometric methods has been presented. Deconvolution of two-way chromatographic signals of nine herbal slimming pills into pure chromatographic and spectral patterns was performed. The peak clusters were resolved using multivariate curve resolution-alternating least squares (MCR-ALS) by employing appropriate constraints. It was revealed that more useful chemical information about the composition of the slimming pills can be obtained by employing sophisticated GC-MS method coupled with proper chemometric tools yielding the extended number of identified constituents. The thorough fingerprinting of the complex mixtures proved the presence of some toxic or carcinogen components, such as toluene, furfural, furfuryl alcohol, styrene, itaconic anhydride, citraconic anhydride, trimethyl phosphate, phenol, pyrocatechol, p-propenylanisole and pyrogallol. In addition, some samples were shown to be adulterated with undeclared ingredients, including stimulants, anorexiant and laxatives such as phenolphthalein, amfepramone, caffeine and sibutramine.

Chemometrics-assisted chromatographic fingerprinting: An illicit methamphetamine case study.

The volatile chemical constituents in complex mixtures can be analyzed using gas chromatography with mass spectrometry. This analysis allows the tentative identification of diverse impurities of an illicit methamphetamine sample. The acquired two-dimensional data of liquid-liquid extraction was resolved by multivariate curve resolution alternating curve resolution to elucidate the embedded peaks effectively. This is the first report on the application of a curve resolution approach for chromatogram fingerprinting to identify particularly the embedded impurities of a drug of abuse. Indeed, the strong and broad peak of methamphetamine makes identifying the underlying peaks problematic and even impossible. Mathematical separation instead of conventional chromatographic approaches was performed in a way that trace components embedded in methamphetamine peak were successfully resolved. Comprehensive analysis of the chromatogram, using multivariate curve resolution, resulted in elution profiles and mass spectra for each pure compound. Impurities such as benzaldehyde, benzyl alcohol, benzene, propenyl methyl ketone, benzyl methyl ketone, amphetamine, N-benzyl-2-methylaziridine, phenethylamine, N,N,α-trimethylamine, phenethylamine, N,α,α-trimethylmethamphetamine, N-acetylmethamphetamine, N-formylmethamphetamine, and other chemicals were identified. A route-specific impurity, N-benzyl-2-methylaziridine, indicating a synthesis route based on ephedrine/pseudoephedrine was identified. Moreover, this is the first report on the detection of impurities such as phenethylamine, N,α,α-trimethylamine (a structurally related impurity), and clonitazene (as an adulterant) in an illicit methamphetamine sample.

Chemometrics-Assisted Fast-Elution HPLC-DAD for the Quantification of Selected UV Filters and Parabens in Suncare Formulations.

In the present study, a fast LC method coupled with multivariate curve resolution (MCR) alternating least-squares (ALS) and alternating trilinear decomposition (ATLD) was developed for the determination of the resolution of and quantitation of benzophenone-3, 4-methylbenzylidene camphor, octocrylene, ethylhexyl dimethyl para-aminobenzoic acid, butyl methoxydibenzoilmethane, and methyl and propyl parabens in suncare products. Chromatographic separation was optimized using full factorial and Box-Behnken designs. MCR-ALS and ATLD performance in quantitating the analytes in synthetic mixtures (which were randomly prepared in ultra-pure water) and blank sunscreen products was studied, and satisfying results were obtained. Acceptable qualification and quantification results were also achieved in the presence of matrix interferences via a short chromatographic runtime (5 min), and the second-order advantage was fully exploited, with MCR-ALS clearly emerging as the superior model. Average recoveries ranged from 98.0 to 112.5%, and RSD values were lower than 6.5%. LODs between 0.066 and 0.243 µg/g were achieved. In addition to acceptable precision and accuracy, the merits of the proposed method are that the analysis is fast and there is minimal solvent consumption. Moreover, coelution of analytes and interference from components in the sample matrixes were overcome with multivariate analysis.

Surfactant-assisted dispersive liquid-liquid microextraction of nitrazepam and lorazepam from plasma and urine samples followed by high-performance liquid chromatography with UV analysis.

Surfactant-assisted liquid-liquid microextraction followed by high-performance liquid chromatography with UV detection has been developed for the simultaneous preconcentration and determination of lorazepam and nitrazepam in biological fluids. In this study, an ionic surfactant (cetyltrimethyl ammonium bromide) was used as an emulsifier. The predominant parameters affecting extraction efficiency such as the type and volume of extraction solvent, the type and concentration of surfactant, sample pH, and the concentration of salt added to the sample were investigated and opted. Under the optimum conditions (extraction solvent and its volume, 1-octanol, 70 µL; surfactant and its concentration, 1 mL of ultra-pure water containing 2 mmol L-1 cetyltrimethyl ammonium bromide; sample pH = 9 and salt content of 10% NaCl w/v), the preconcentration factors were obtained in the range of 202-241 and 246-265 for nitrazepam and lorazepam, respectively. The limits of quantification for both drugs were 5 µg L-1 in water sample and 10 µg L-1 in biological fluids with R2 values higher than 0.993. The suitability of the proposed method was successfully confirmed by the extraction and determination of the target drugs in human urine and plasma samples in the range of microgram per liter.

Polypyrrole/magnetic nanoparticles composite as an efficient sorbent for dispersive micro-solid-phase extraction of antidepressant drugs from biological fluids.

In this study, polypyrrole/magnetic nanoparticles composites in the presence of two different dopants were synthesized with the aid of chemical oxidative polymerization process for dispersive-µ-solid phase extraction (D-µ-SPE). The synthesized magnetic sorbents were characterized by various techniques. The results exhibited that the nanocomposite modified by polypyrrole with sodium perchlorate as a dopant demonstrated higher extraction efficiency for citalopram (CIT) and sertraline (STR) as the model compounds. This nanosorbent in combination with high performance liquid chromatography-UV detection was applied for extraction, preconcentration and determination of CIT and STR in urine and plasma samples. The effect of various parameters on the extraction efficiency including: sample pH, amount of sorbent, sorption time, eluent and its volume, salt content, and elution time were investigated and optimized. The opted conditions were: sample pH, 9.0; sorbent dosage, 10mg; sorption time, 7 min; elution solvent and its volume, 0.06 mol L(-1) HCl in methanol, 120 µL; elution time, 2 min and without addition of salt to the sample. The calibration curves were linear in the concentration range of 1-800 µg L(-1). The limits of detection (LODs) were obtained in the range of 0.2-1.0 µg L(-1) for CIT and 0.3-0.7 µg L(-1) for STR, respectively. The percent of extraction recoveries and relative standard deviations (n=5) were in the range of 93.4-99, 4.8-8.4 for CIT and 94-98.4, 4.3-9.2 for STR, respectively. Finally, the applicability of the method was successfully confirmed by the extraction and determination of CIT and STR in human urine and plasma samples.

Synthesis, characterisation and analytical application of Fe3O4@SiO2@polyaminoquinoline magnetic nanocomposite for the extraction and pre-concentration of Cd(II) and Pb(II) in food samples.

This work describes a novel Fe3O4@SiO2@polyaminoquinoline magnetic nanocomposite and its application in the pre-concentration of Cd(II) and Pb(II) ions. The parameters affecting the pre-concentration procedure were optimised by a Box-Behnken design through response surface methodology. Three variables (extraction time, magnetic sorbent amount and pH) were selected as the main factors affecting the sorption step, while four variables (type, volume and concentration of the eluent, and elution time) were selected as main factors in the optimisation study of the elution step. Following the sorption and elution of analytes, the ions were quantified by flame atomic absorption spectrometry (FASS). The limits of detection were 0.1 and 0.7 ng ml(-1) for Cd(II) and Pb(II) ions, respectively. All the relative standard deviations were less than 7.6%. The sorption capacities of this new sorbent were 57 mg g(-)(1) for Cd(II) and 73 mg g(-1) for Pb(II). Ultimately, this nanocomposite was successfully applied to the rapid extraction of trace quantities of these heavy metal ions from seafood and agricultural samples and satisfactory results were obtained.

Solid phase extraction of Cd(II) and Pb(II) ions based on a novel functionalized Fe3O4@ SiO2 core-shell nanoparticles with the aid of multivariate optimization methodology.

This work describes novel Fe3O4@SiO2 core-shell nanoparticles functionalized with phenyl isothiocyanate and its application in the preconcentration of Cd(II) and Pb(II) ions. The parameters affecting the preconcentration procedure were optimized by a Box-Behnken design through response surface methodology. Three variables (extraction time, magnetic sorbent amount, and pH value) were selected as the main factors affecting the sorption step, while four variables (type, volume and concentration of the eluent; and elution time) were selected as effective factors of elution step in the optimization study. Following the sorption and elution, the ions were quantified by FAAS. The limits of detection were 0.05 and 0.9ngmL(-1) for Cd(II) and Pb(II) ions, respectively. The relative standard deviations were less than 6.4%. The sorption capacity (in mg g(-1)) of this new sorbent is 179 for Cd(II) and 156 for Pb(II). Finally, this nanocomposite was successfully applied to the rapid extraction of trace quantities of heavy metal ions from fish, sediment, soil, and water samples and satisfactory results were obtained.

Dispersive micro-solid-phase extraction of benzodiazepines from biological fluids based on polyaniline/magnetic nanoparticles composite.

In this study, diverse types of Fe3O4 nanocomposites modified by polyaniline, polypyrrole, and aniline-pyrrole copolymer were synthesized through chemical oxidative polymerization process for dispersive-µ-solid phase extraction (D-µ-SPE) in the presence of various dopants. The results showed that the nanocomposite modified by polyaniline with p-toluene sulfonic acid as a dopant demonstrated higher extraction efficiency for lorazepam (LRZ) and nitrazepam (NRZ). Also the synthesized magnetic sorbents were characterized. The nanocomposite sorbent in combination with high performance liquid chromatography-UV detection was applied for the extraction, preconcentration and determination of lorazepam and nitrazepam in urine and plasma samples. Different parameters influencing the extraction efficiency including: sample pH, amount of sorbent, sorption time, elution solvent and its volume, salt content, and elution time were optimized. The obtained optimal conditions were: sample pH, 6; amount of sorbent, 5 mg; sorption time, 5.0 min; elution solvent and its volume, 0.5 mM cethyltrimethyl ammonium bromide in acetonitrile, 150 µL; elution time, 2.0 min and without addition of NaCl. The calibration curves were linear in the concentration range of 1-2000 µg L(-1). The limits of detection (LODs) were achieved in the range of 0.5-1.8 µg L(-1) for NRZ and 0.2-2.0 µg L(-1) for LRZ, respectively. The percent of extraction recoveries and relative standard deviations (n=5) were in the range of 84.0-99.0, 6.1-7.8 for NRZ and 90.0-99.0, 4.1-7.0 for LRZ, respectively. Ultimately, the applicability of the method was successfully confirmed by the extraction and determination of NRZ and LRZ in human urine and plasma samples.

A novel 4-(2-pyridylazo) resorcinol functionalised magnetic nanosorbent for selective extraction of Cu(II) and Pb(II) ions from food and water samples.

This paper describes a novel sorbent based on 4-(2-pyridylazo) resorcinol functionalised magnetic nanoparticles and its application for the extraction and pre-concentration of trace amounts of Cu(II) and Pb(II) ions. The nanosorbent was characterised by Fourier transform infrared spectroscopy, X-ray powder diffraction, thermal analysis, elemental analysis and scanning electron microscopy. The effects of various parameters such as pH, sorption time, sorbent dosage, elution time, volume and concentration of eluent were investigated. Following the sorption and elution of analytes, Cu(II) and Pb(II) ions were quantified by flame atomic absorption spectrometry. The limits of detection were 0.07 and 0.7 µg l(-1) for Cu(II) and Pb(II), respectively. The relative standard deviations of the method were less than 7%. The sorption capacity of this new sorbent were 92 and 78 mg g(-1) for Cu(II) and Pb(II), respectively. Finally this nanosorbent was applied to the rapid extraction of trace quantities of Cu(II) and Pb(II) ions in different real samples and satisfactory results were obtained.

Magnetic nanoparticles based dispersive micro-solid-phase extraction as a novel technique for coextraction of acidic and basic drugs from biological fluids and waste water.

The coextraction of acidic and basic drugs from different samples is a considerable and disputable concept in sample preparation strategies. In this study, for the first time, simultaneous extraction of acidic and basic drugs with magnetic nanoparticles based dispersive micro-solid phase extraction followed by high performance liquid chromatography-ultraviolet detection was introduced. Cetyltrimethyl ammonium bromide-coated Fe3O4@decanoic acid as an efficient sorbent was successfully applied to adsorb diclofenac (DIC) as an acidic and diphenhydramine (DPH) as a basic model compound. First, appropriate amount of synthetic Fe3O4@decanoic acid nanoparticles was added to aqueous solution of drugs. After adjusting the pH of the solution, cetyltrimethyl ammonium bromide (CTAB) was added to the mixture being stirred at a constant rate. After the adsorption of drugs and decantation of supernatant with a magnetic field, the sorbent was eluted with methanol by fierce vortex. The parameters affecting the extraction efficiency were optimized and obtained as: pH of the sample=9, concentration of CTAB=0.2mmolL(-1), amount of sorbent=10mg, extraction time=5min, no salt addition to sample, type and volume of the eluent=50µL methanol, and desorption time=1min. Under the optimum conditions detection limits and linear dynamic ranges were achieved in the range of 1.8-3.0, 5-1500µgL(-1) for DPH and 1.5-3.5, 5-1500µgL(-1) for DIC, respectively. The percent of extraction recovery and relative standard deviations (n=5) were in the range of 47.3-60, 5.2-9.0 for DPH and 64-76.7, 5.1-5.8 for DIC, respectively. Ultimately, the applicability of the method was successfully confirmed by the extraction and determination of DIC and DPH in human urine, plasma and waste water samples in the range of microgram per liter and satisfactory results were obtained.

Optimization of solvent bar microextraction combined with gas chromatography for preconcentration and determination of methadone in human urine and plasma samples.

In this study, solvent bar microextraction combined with gas chromatography-flame ionization detector (GC-FID) was used for preconcentration and determination of methadone in human body fluids. The target drug was extracted from an aqueous sample with pH 11.5 (source phase) into an organic extracting solvent (1-Undecanol) located inside the pores and lumen of a polypropylene hollow fiber as a receiving phase. To obtain high extraction efficiency, the effect of different variables on the extraction efficiency was studied using an experimental design. The variables of interest were the organic phase type, source phase pH, ionic strength, stirring rate, extraction time, concentration of Triton X-100, and extraction temperature, which were first investigated by Plackett-Burman design and subsequently by central composite design (CCD). So that the optimum experimental condition was obtained when the sodium chloride concentration was 5% (w/v); stirring rate, 700 rpm; extraction temperature, 20 °C; extraction time, 45 min and pH of the aqueous sample, 11.5. Under the optimized conditions, the preconcentration factors were between 275 and 300. The calibration curves were linear in the concentration range of 10-1500 µg L(-1). The limits of detection (LODs) were 2.7-7 and relative standard deviations (RSDs) of the proposed method were 5.9-7.3%. Ultimately, the applicability of the current method was evaluated by the extraction and determination of methadone in different biological samples.

Multivariate optimization of surfactant-assisted directly suspended droplet microextraction combined with GC for the preconcentration and determination of tramadol in biological samples.

In this work, a novel procedure based on surfactant-assisted directly suspended droplet microextraction for the determination of tramadol prior to GC with flame ionization detection is proposed. In this technique, a free microdroplet of solvent is transferred to the surface of an immiscible aqueous sample containing Triton X-100 and tramadol while being agitated by a stirring bar placed on the bottom of the sample vial. After the predetermined time, the microdroplet of solvent is withdrawn by a syringe and analyzed. The effective parameters such as the type of organic solvent, extraction time, microdroplet volume, salt content of the donor phase, stirring speed, the source phase pH, concentration of Triton X-100, and extraction temperature were optimized. For this purpose, a multivariate strategy was applied based on an experimental design in order to screen and optimize the significant factors. This method requires minimal sample preparation, analysis time, solvent consumption, and represents significant advantages over customary analytical methods. The linearity ranged from 10 to 2000 µg/L with RSDs (n = 5) of 7.3-10. Preconcentration factors and the LODs were 391-466 and 2.5-6.5 µg/L, respectively. Finally, this method was applied to the analysis of biological samples and satisfactory results were obtained.

Determination of haloperidol in biological samples using molecular imprinted polymer nanoparticles followed by HPLC-DAD detection.

In this study an extraction procedure using molecular imprinted polymer nanoparticles for the determination of haloperidol in biological samples is proposed. The haloperidol imprinted polymer nanoparticles were synthesized successfully by precipitation polymerization in a flask containing haloperidol as a template, ethyleneglycoldimethacrylate as a crosslinking agent, methacrylic acid as a functional monomer, and 2,2'-azobisisobutyronitrile as an initiator. The leached and unleached polymer nanoparticles have been characterized by infrared spectroscopy and scanning electron microscopy. The effect of different variables such as the pH of solution, uptake and elution time, type, and the least amount of eluent for elution of haloperidol from polymer was evaluated. Extraction efficiencies more than 97% were obtained by elution of the polymer with 1.5 mL of methanol-acetic acid-trifluoroacetic acid 79.9:20:0.1. Under optimal conditions maximum adsorption capacity was obtained 153.84 mg g(-1). The detection limit of the proposed procedure was between 0.2 and 0.35 µg L(-1). Finally this method was applied to the determination of haloperidol in plasma and urine samples and satisfactory results were achieved (RSD<6.9%).

Determination of haloperidol in biological samples with the aid of ultrasound-assisted emulsification microextraction followed by HPLC-DAD.

A rapid and simple quantitative method for preconcentration and determination of haloperidol in biological samples was developed using ultrasound-assisted emulsification microextraction, based on the solidification of floating organic droplet combined with HPLC-DAD. The effects of several factors were investigated. A total of 30 µL of 1-undecanol as an extraction solvent was injected slowly into a glass-centrifuge tube containing 4 mL alkaline sample solution that was located inside the ultrasonic water bath. The formed emulsion was centrifuged and the fine droplets of solvent were floated at the top of the test tube, then it was cooled in an ice bath and the solidified solvent was transferred into a conical vial, after melt, the analysis of the extract was carried out by HPLC. Under the optimal conditions, the extraction efficiencies were more than 90% and the preconcentration factors were obtained between 119-122. The LOQs were obtained between 4-8 µg/L and the calibration curves were linear within the range of 4-1000 µg/L. Finally this method was applied to the determination of haloperidol in plasma and urine samples in the range of µg/L and satisfactory results were achieved (RSDs <7%).

Optimization of ion-pair based hollow fiber liquid phase microextraction combined with HPLC-UV for the determination of methimazole in biological samples and animal feed.

Ion-pair based hollow fiber liquid phase microextraction (IP-HFLPME) coupled with high performance liquid chromatography-ultraviolet detection was applied for the preconcentration and determination of methimazole in biological samples and animal feed. Optimization of the conditions for the high extraction efficiency was studied simultaneously using the experimental design. For the first step, the Plackett-Burman design was applied to screen the significant factors on the extraction efficiency. Central composite design (CCD) was then used for the optimization of important factors and the response surface equations were obtained. The optimum experimental conditions were donor phase pH, 12.2; extraction temperature, 45°C; extraction time, 50 min; sodium perchlorate concentration, 1.5 M; cetyltrimethylammonium bromide concentration, 0.65 mM, and without salt addition in donor phase. The limit of detection and the dynamic linear range were in the range of 0.1-0.7 µg L(-1) and 0.5-1000 µg L(-1), respectively. Preconcentration factors were obtained in the range of 93-155 in different matrices. Finally, the performance of the proposed method was tested for the determination of trace amounts of methimazole in plasma, urine, bovine milk, and animal feed samples, and satisfactory results were obtained (RSDs < 7.1%).

Simultaneous determination of chloropheniramine maleate and dextromethorphan hydrobromide in plasma sample by hollow fiber liquid phase microextraction and high performance liquid chromatography with the aid of chemometrics.

A simple and high sensitive technique based on three phase hollow fiber liquid phase microextraction (HF-LPME), optimized by using a four-variable experimental design and response surface methodology was performed to evaluate dextromethorphan hydrobromide (DEX) and chloropheniramine maleate (CLP) simultaneously in human plasma. The influence of source phase pH, HCl concentration of acceptor phase, time and salt addition were investigated. Under the optimized conditions analytes were extracted in their neutral form, pH 12.5 and salt concentration 2% (w/v), through a supported liquid membrane (SLM) of hexadecane into the HCl 0.0005 mol L(-1) located inside the lumen of hollow fiber to be back extracted. The mass transfer of the analytes from the donor phase through the SLM into acceptor phase was driven by the pH gradient. Determination was accomplished by UV-high performance liquid chromatography with recoveries 92% and 84% for CLP and DEX, respectively. Linearity was obtained in the range of 0.01-1000 µg L(-1) (R(2)>0.994). The obtained enrichment factors (EFs) were 233-276 for DEX and CLP respectively and limits of detection were 0.003 µg L(-1) with RSDs below 6%. The method proposed acceptable values to determine CLP and DEX in plasma samples sensitively and accurately.