Hamid Reza Sobhi

Comparison between a high-resolution single-stage Orbitrap and a triple quadrupole mass spectrometer for quantitative analyses of drugs

The capabilities of a high-resolution (HR), accurate mass spectrometer (Exactive-MS) operating in full scan MS mode was investigated for the quantitative LC/MS analysis of drugs in patients plasma samples. A mass resolution of 50,000 (FWHM) at m/z 200 and a mass extracted window of 5u2009ppm around the theoretical m/z of each analyte were used to construct chromatograms for quantitation. The quantitative performance of the Exactive-MS was compared with that of a triple quadrupole mass spectrometer (TQ-MS), TSQ Quantum Discovery or Quantum Ultra, operating in the conventional selected reaction monitoring (SRM) mode. The study consisted of 17 therapeutic drugs including 8 antifungal agents (anidulafungin, caspofungin, fluconazole, itraconazole, hydroxyitraconazole posaconazole, voriconazole and voriconazole-N-oxide), 4 immunosuppressants (ciclosporine, everolimus, sirolimus and tacrolimus) and 5 protein kinase inhibitors (dasatinib, imatinib, nilotinib, sorafenib and sunitinib). The quantitative results obtained with HR-MS acquisition show comparable detection specificity, assay precision, accuracy, linearity and sensitivity to SRM acquisition. Importantly, HR-MS offers several benefits over TQ-MS technology: absence of SRM optimization, time saving when changing the analysis from one MS to another, more complete information of what is in the samples and easier troubleshooting. Our work demonstrates that U/HPLC coupled to Exactive HR-MS delivers comparable results to TQ-MS in routine quantitative drug analyses. Considering the advantages of HR-MS, these results suggest that, in the near future, there should be a shift in how routine quantitative analyses of small molecules, particularly for therapeutic drugs, are performed.

Suitable conditions for liquid-phase microextraction using solidification of a floating drop for extraction of fat-soluble vitamins established using an orthogonal array experimental design

A simple, rapid and efficient microextraction method for the extraction and determination of some fat-soluble vitamins (A, D2, D3) in aqueous samples was developed. For the first time orthogonal array designs (OADs) were employed to screen the liquid-phase microextraction (LPME) method in which few microliters of 1-undecanol were delivered to the surface of the aqueous sample and it was agitated for a selected time. Then sample vial was cooled by inserting it into an ice bath for 5 min. The solidified solvent was transferred into a suitable vial and immediately melted. Then, the extract was directly injected into a high-performance liquid chromatography (HPLC) for analysis. Several factors affecting the microextraction efficiency such as sample solution temperature, stirring speed, volume of the organic solvent, ionic strength and extraction time were investigated and screened using an OA16 (4(5)) matrix. Under the best conditions (temperature, 55 degrees C; stirring speed, 1000 rpm; the volume of extracting solvent, 15.0 microL; no salt addition and extraction time, 60 min), detection limits of the method were in the range of 1.0-3.5 microgL(-1). The relative standard deviations (RSDs) to determine the vitamins at microg L(-1) levels by applying the proposed method varied in the range of 5.1-10.7%. Dynamic linear ranges of 5-500 mugL(-1) with good correlation coefficients (0.9984<r(2)<0.9991) were observed. Finally, the study was applied to determine the vitamins in several real aqueous samples including mixed juice fruit, urine and tap water samples and relatively good results were obtained.

Quantitation of mononitrotoluenes in aquatic environment using dispersive liquid–liquid microextraction followed by gas chromatography–flame ionization detection

A simple and efficient method (known as dispersive liquid-liquid microextraction (DLLME)) combined with gas chromatography-flame ionization detector (GC-FID) has been successfully developed for the extraction and determination of mononitrotoluenes (MNTs) in aquatic samples. The effects of parameters such as the nature and volume of the extracting and disperser solvents on the microextraction efficiency were also investigated. The volume of the extracting solvent (chlorobenzene) and that of the disperser solvent (acetonitrile) were obtained to be equal to 10.0 microL and 0.5 mL, respectively, in the optimal microextraction conditions established. Under the optimal conditions, the detection limit of the method was 0.5 microg L(-1) and the relative standard deviations (RSDs%) for determination of the MNTs were in the range of 8.0-9.4. Linearity was found to be in the range of 1-1000 microg L(-1); also, the pre-concentration factors were in the range of 351-357. Finally, the method was applied to determine the trace amounts of the MNTs in several real aquatic samples and satisfactory results were obtained.

Solid drop based liquid-phase microextraction

Solid drop based liquid-phase microextraction (SDLPME) is a novel sample preparation technique possessing obvious advantages of simple operation with a high pre-concentration factor, low cost and low consumption of organic solvent. SDLPME coupled with gas chromatography (GC), high-performance liquid chromatography (HPLC), and atomic absorption spectrometry (AAS) has been widely applied to the analyses of a different variety of samples. The basic principles, parameters affecting the extraction efficiency, and the latest applications of SDLPME are reviewed in this article.

Extraction and determination of 2-pyrazoline derivatives using liquid phase microextraction based on solidification of floating organic drop.

A simple, rapid and efficient microextraction method for the extraction and determination of some 2-pyrazoline derivative compounds in aqueous samples was developed. Microliter volumes of 1-undecanol were delivered to the surface of the aqueous sample and the sample was agitated for a desire time. The sample vial was cooled by inserting it into an ice bath for 5 min. The solidified solvent was transferred into a suitable vial and immediately melted. One microL of the organic solvent was injected into a gas chromatography (GC) for analysis. Several factors affecting the microextraction efficiency such as sampling temperature, stirring rate, pH, nature and volume of the organic solvent and extraction time were investigated and optimized values were obtained as 70 degrees C, ,1250 rpm, 5.0, 8.0 microL (1-undecanol) and 30 min, respectively. Under the optimal conditions, detection limits of the method for determination of the compounds were in the range of 5-10 microgL(-1). The relative standard deviations (RSDs%) for the extraction and determination of the analytes at the concentration level of 250 microgL(-1) were in the range of 3.0-11.4. Dynamic linear ranges of 25-800 microgL(-1) with correlation coefficients in the range of 0.9857<r(2)<0.9968 were observed. After 30 min of extraction duration, the enrichment factors varied from 183 to 538. Finally, the study was applied to the determination of the compounds in several real samples including serum and urine and satisfactory results were obtained.

Quantitation of antioxidants in water samples using ionic liquid dispersive liquid–liquid microextraction followed by high‐performance liquid chromatography‐ultraviolet detection

A simple and efficient method, ionic liquid-based dispersive liquid-liquid microextraction combined with high-performance liquid chromatography-ultraviolet detection (HPLC-UV), has been applied for the extraction and determination of some antioxidants (Irganox 1010, Irganox 1076 and Irgafos 168) in water samples. The microextraction efficiency factors were investigated and optimized: 1-hexyl-3-methylimidazolium hexafluorophosphate [C(6)MIM][PF(6)] (0.06 g) as extracting solvent, methanol (0.5 mL) as disperser solvent without salt addition. Under the selected conditions, enrichment factors up to 48-fold, limits of detection (LODs) of 5.0-10.0 ng/mL and dynamic linear ranges of 25-1500 ng/mL were obtained. A reasonable repeatability (RSD≤11.8%, n=5) with satisfactory linearity (r(2)≥0.9954) of the results illustrated a good performance of the presented method. The accuracy of the method was tested by the relative recovery experiments on spiked samples, with results ranging from 85 to 118%. Finally, the method was successfully applied for determination of the analytes in several real water samples.

Highly Selective and Sensitive Triiodide PVC‐Based Membrane Electrode Based on a New Charge Transfer Complex of 2‐(((2‐(((E)‐1‐(2‐Hydroxyphenyl) Methylidine) Amino) Phenyl) Imino) Methyl) Phenol for Nano‐Level Monitoring of Triiodide

Abstract A highly selective and sensitive triiodide sensor based on a 2‐(((2‐(((E)‐1‐(2‐hydroxy phenyl) methylidine) amino) phenyl) imino) methyl) phenol with iodine (CTC) as membrane carrier was developed. The electrode revealed a Nernstian behavior over a very wide triiodide‐ion concentration range (5.0×10−8–1.0×10−2 M), and relatively low detection limit (3.0×10−8 M). The potentiometric response is independent of the pH of solution in the pH range of 3.0–10.0. The electrodes manifest advantages of low resistance, very fast response (<12 s), and most importantly, good selectivities relative to a wide variety of inorganic and organic anions, including iodide, bromide, chloride, fluoride, sulfite, sulfate, cyanide, thiocyanate, and acetate. In fact, the selectivity behavior of the proposed triiodide ion‐selective electrode shows great improvements compared to the previously reported electrodes for the triiodide ion. The proposed membrane sensor can be used for at least 6 months without any significant divergences in the potential. The electrode was successfully applied as an indicator electrode in the titration of triiodide with thiosulfate ion.

Tandem use of solid-phase extraction and dispersive liquid–liquid microextraction for the determination of mononitrotoluenes in aquatic environment

Solid-phase extraction (SPE) in tandem with dispersive liquid-liquid microextraction (DLLME) has been developed for the determination of mononitrotoluenes (MNTs) in several aquatic samples using gas chromatography-flame ionization (GC-FID) detection system. In the hyphenated SPE-DLLME, initially MNTs were extracted from a large volume of aqueous samples (100u2009mL) into a 500-mg octadecyl silane (C(18)) sorbent. After the elution of analytes from the sorbent with acetonitrile, the obtained solution was put under the DLLME procedure, so that the extra preconcentration factors could be achieved. The parameters influencing the extraction efficiency such as breakthrough volume, type and volume of the elution solvent (disperser solvent) and extracting solvent, as well as the salt addition, were studied and optimized. The calibration curves were linear in the range of 0.5-500u2009μg/L and the limit of detection for all analytes was found to be 0.2u2009μg/L. The relative standard deviations (for 0.75u2009μg/L of MNTs) without internal standard varied from 2.0 to 6.4% (n=5). The relative recoveries of the well, river and sea water samples, spiked at the concentration level of 0.75u2009μg/L of the analytes, were in the range of 85-118%.

Quantitation of valproic acid in pharmaceutical preparations using dispersive liquid-liquid microextraction followed by gas chromatography-flame ionization detection without prior derivatization.

Dispersive liquid-liquid microextraction (DLLME), coupled with gas chromatography-flame ionization detection (GC-FID), has been successfully used for the extraction and determination of valproic acid (VPA) in pharmaceutical preparations. In the developed method, an appropriate mixture of extracting and disperser solvents was rapidly injected into an aqueous sample. Having formed a cloudy solution, the mixture was centrifuged and then the extracting solvent was sedimented at the bottom of a conical test tube. The extract was then injected into a GC system directly, without any further pretreatment. Initially, microextraction efficiency factors were optimized and the optimum experimental conditions found were as follows: tetrachloroethylene (9.0 µL) as extracting solvent; acetone (1.0 mL) as disperser solvent; 5 mL acidic aqueous sample (pH 1) without salt addition. Under the selected conditions, the calibration curve showed linearity in the range of 0.1-5.0 mg/L with regression coefficient corresponding to 0.9998. The limit of detection was found to be 0.05 mg/L. Finally, the method was applied for the determination of VPA in two different pharmaceutical preparations. A reasonable intra-assay (3.9-10.8%, n = 3) and inter-assay (5.6-11.4%, n = 3) precision illustrated the good performance of the analytical procedure. The protocol proved to be rapid and cost-effective for screening purposes.

Determination of trace amounts of some low molecular weight alcohols in aqueous samples using liquid-phase microextraction and gas chromatography

A new and versatile liquid-phase microextraction method combined with gas chromatography (GC) analysis was applied for the extraction and determination of some aliphatic alcohols. Microlitre volumes of 1-undecanol were delivered on to the surface of the aqueous sample and the sample was agitated for a desired time. Then, the sample vial was cooled by inserting it into an ice bath for 5 min. The solidified solvent was transferred into a suitable vial and immediately melted, of which 1.0 µL was injected into GC for analysis. The parameters affecting the microextraction efficiency such as sampling temperature, stirring rate, nature and volume of the extracting solvent, salt addition and extraction time were investigated. The optimal microextraction conditions were established as: sample solution temperature, 60°C; stirring rate, 1250 rpm; volume of the extracting solvent, 8.0 µL (1-undecanol); salt concentration, 4 M NaCl and extraction time of 20 min. Under the optimal conditions, detection limits of the method were in the range of 3–56 µg L−1 and the relative standard deviations for determination of the alcohols were in the range of 2.2–11.9. Dynamic linearity of the alcohols was found to be in the range of 60–800 µg L−1. After 20 min of extraction period, the pre-concentration factors for the alcohols were in the range of 13–358. Finally, the method was applied for determination of trace amounts of the alcohols in several real aqueous samples and satisfactory results were obtained.