Synthesis of zinc oxide powders in plasma–solution systems

A new method is proposed for the synthesis of powdered zinc oxide with the use of a plasma–solution system. The chemical and phase compositions and the morphology of the synthesized powders have been determined. It has been found that the calcination of powders obtained in the plasma–solution system leads to the formation of ZnO.     

Validated HPLC–MS–MS method for determination of azithromycin in human plasma

A validated, highly sensitive, and selective HPLC method with MS–MS detection has been developed for quantitative determination of azithromycin (AZI) in human Na₂EDTA plasma. Roxithromycin (ROX) was used as internal standard. Human plasma containing AZI and internal standard was ultrafiltered through Centrifree Micropartition devices and the concentration of AZI was determined by isocratic HPLC–MS–MS. Multiple reaction monitoring mode (MRM) was used for MS–MS detection. The calibration plot was linear in the concentration range 2.55–551.43 ng mL⁻¹. Inter-day and Intra-day precision and accuracy of the proposed method were characterized by R.S.D and percentage deviation, respectively; both were less than 8%. Limit of quantification was 2.55 ng mL⁻¹. The proposed method was used to determine the pharmacokinetic profile of AZI (250-mg tablets).     

Liquid chromatography–mass spectrometric determination of plasmalogens in human plasma

A new liquid chromatography–mass spectrometry (LC/MS) method has been developed for the quantitative analysis of plasmalogens in human plasma using a nonendogenous plasmalogen (1-O-1′-(Z)-tricosenyl-2-oleoyl-rac-glycero-3-phosphocholine, PLS 23:0/18:1) as an internal standard. 1-O-1′-(Z)-Tricosenyl glyceryl ether was prepared by reacting lithioalkoxyallyl with 1-iodoeicosane as the key intermediate in the formation of PLS 23:0/18:1. In LC/MS analyses, PLS 23:0/18:1 generated significant fragment ions in positive and negative modes. In positive ion mode, the [M+H]⁺ of PLS 23:0/18:1 yielded unique fragments with cleavages at the sn-1 and sn-2 positions of the glycerol backbone. In negative ion mode, the [M+CH₃COO]⁻ of PLS 23:0/18:1 resulted in characteristic fragmentation at the sn-2 and sn-3 positions. 1-O-1′-(Z)-Hexadecenyl-2-linoleoyl-rac-glycero-3-phosphocholine (PLS 16:0/18:2) and 2-arachidonoyl-O-1′-(Z)-hexadecenyl-rac-glycero-3-phosphocholine (PLS 16:0/20:4) were chemically synthesized as PLS 23:0/18:1. The calibration curves obtained for PLS 16:0/18:2 and PLS 16:0/20:4 were linear throughout the calibration range (0.04–1.60 pmol). The LOD (S/N = 5:1) was 0.008 pmol and the LOQ (S/N = 6:1) was 0.01 pmol for both PLS 16:0/18:2 and PLS 16:0/20:4. Plasma concentrations of PLS 16:0/18:2 and PLS 16:0/20:4 were 4.0 ± 1.3 μM and 3.5 ± 1.2 μM (mean ± SD), respectively, in five healthy volunteers.     

Direct elemental analysis of biodiesel by inductively coupled plasma–mass spectrometry

An ICP–MS instrument fitted with an octopole reaction system (ORS) was used to directly measure the inorganic contents of several biofuel materials. Following sample preparation by simple dilution in kerosene, the biofuels were analysed directly. The ORS effectively removed matrix- and plasma-based spectral interferences to enable measurement of all important analytes, including sulfur, at levels below those possible by ICP–OES. A range of commonly produced biofuels was analysed, and spike recovery and long-term stability data was acquired. Suitably configured ICP–MS has been shown to be a fast and very sensitive technique for the elemental analysis of biofuels.     

Study of titanocene–DNA and molybdenocene–DNA interactions by inductively coupled plasma–atomic emission spectroscopy

Titanocene and molybdenocene dichlorides belong to a new class of organometallic antitumor agent. Although these complexes are isostructural, they behave differently under physiological conditions and hence have different mechanisms of action. It was initially proposed that these species interact with DNA, inhibiting the cell cycle. Recent studies using nucleotides and oligonucleotides suggest that molybdenocene does not bind DNA constituents at physiological pH whereas titanocene apparently interacts weakly with nucleotides through the phosphoesters. The evidence for this was, however, obtained under non-physiological conditions. Herein we report an analytical method that enables determination of the amount of metal bound to DNA under physiological conditions (pH 7.4 and buffer solution) and with sample preparation (dialysis) that resembles the cell environment. It was found that more than 90% titanium was bound to DNA after 46 h whereas binding of molybdenum was no more than 5%.     

Quantification of water and plasma diagnosis for electrothermal vaporization–inductively coupled plasma–mass spectrometry: the use of argon and argide polyatomics as probing species

The water content of the carrier flow originating from an electrothermal vaporization unit (ETV) attached to an inductively coupled plasma mass spectrometer was monitored by following the argon hydride ion (ArH⁺) at m/z=37. The goal was to measure the water expelled by the ETV at sample vaporization and evaluate the influence of this parameter on the ion-generation efficiency. Linear responses from the argon hydride were obtained when the water loading in the plasma injector flow was increased from 0 to 3.3 mg/min. Other argides and water-derived species (Ar⁺, Ar⁺₂ and O⁺₂) were also monitored simultaneously and the effects from operating parameters have been calculated for each species. The magnitude of these effects can eventually be used as diagnosis tools. It was also found that signals for zinc, copper, lead, antimony and arsenic were greatly influenced by slight variations in water loading at low water levels. These signal fluctuations are greatly attenuated and transients' shapes restored by convoluting each element transient with the ArH⁺ or Ar⁺₂ curves that were recorded simultaneously. Envisioned applications that would benefit from a water-enhanced signal include spray electrothermal vaporization, direct sample insertion and laser ablation for inductively coupled plasma–mass spectrometry. The argon dimer Ar⁺₂ seems more appropriate for making the correction since it provides a direct insight on the plasma temperature and provides a robust signal.     

Computerized simulation of solute–particle vaporization in an inductively coupled plasma

Recent experiments involving aerosol introduction into the inductively coupled plasma have shown that intact droplets and solute particles cause enormous fluctuations in analyte emission and mass-spectral signals. Here, particle-vaporization kinetics are simulated as a detailed function of the operating conditions, fundamental properties and spatial location in the inductively coupled plasma, and as a function of several of the properties of the particles themselves: diameter, chemical composition and size distribution. These simulations portray the particle vaporization as proceeding nominally linearly with respect to the particle radius when the particles are small, but roughly quadratically with radius when the particles are very large. Further, the heat- and mass-transfer-limited rates of vaporization are roughly equal for the typical gas-temperature range in the plasma tail flame, so that at any height either process might limit the rate of vaporization. This similarity gives rise to a dynamic, competitive picture of plasma vaporization kinetics.     

The calculation of Cs and Rb conductivities in the region of liquid–plasma transition

The conductivity and thermal conductivity of Cs and Rb are calculated in the liquid phase and in the region between the plasma (gas) and the liquid states. The last area is located at the temperatures higher than the critical one, near the critical point. The Ziman formalism originated from the liquid metal theory was used for the calculations. The results of present calculations were compared with available experiments and calculations of other researchers. It was found that the liquid state formalism can be applied to expanded liquid Cs and Rb at densities higher than the critical one, but another type of models is necessary at lower densities.     

Liquid chromatographic–electrospray mass spectrometric determination of cyclosporin A in human plasma

A rapid, sensitive and selective liquid chromatography–mass spectrometry (LC–MS) assay has been developed for determination of cyclosporin A (CyA) in human plasma; cyclosporin B (CyB) was used as internal standard (IS). The method utilized a combination of a column-switching valve and a reversed-phase symmetry column. The mobile phase was a 25:75 (v/v) mixture of 10% aqueous glacial acetic acid and acetonitrile. Running time per single run was less than 10 min. Sample preparation included C₈ SPE of human plasma spiked with the analyte and internal standard, evaporation of the eluate to dryness at 50°C under N₂ gas, and finally reconstitution in the mobile phase. Detection of cyclosporin A and the IS was performed in selected ion-monitoring mode at m/z 601.3 and 594.4 Da for CyA and IS, respectively. Quantitation was achieved by use of the regression equation of relative peak area of cyclosporin to IS against concentration of cyclosporin. The method was validated according to FDA guideline requirements. The linearity of the assay in the range 5.0–400.0 ng mL^–1 was verified as characterized by the least-squares regression line Y=(0.00268±1.9×10^–4)X+(0.00078±1.8×10^–3), correlation coefficient, r=0.9986±1.1×10^–3 (n=48). Intra and inter-day quality-control measurements in the range 5.0–350.0 ng mL^–1 revealed almost 100% accuracy and 9% CV for precision. The mean absolute recovery of CyA was found to be 84.01±9.9% and the respective relative recovery was 100.3±9.19. The limit of quantitation (LOQ) achieved was 5 ng mL^–1. Eventually, stability testing of the analyte and IS in plasma or stock solution revealed that both chemicals were very stable when stored for long or short periods of time at room temperature or –20°C.     

Qualitative detection of desmopressin in plasma by liquid chromatography–tandem mass spectrometry

This work describes a liquid chromatography–electrospray tandem mass spectrometry method for detection of desmopressin in human plasma in the low femtomolar range. Desmopressin is a synthetic analogue of the antidiuretic hormone arginine vasopressin and it might be used by athletes as a masking agent in the framework of blood passport controls. Therefore, it was recently added by the World Anti-Doping Agency to the list of prohibited substances in sport as a masking agent. Mass spectrometry characterization of desmopressin was performed with a high-resolution Orbitrap-based mass spectrometer. Detection of the peptide in the biological matrix was achieved using a triple-quadrupole instrument with an electrospray ionization interface after protein precipitation, weak cation solid-phase extraction and high performance liquid chromatography separation with an octadecyl reverse-phase column. Identification of desmopressin was performed using three product ions, m/z 328.0, m/z 120.0, and m/z 214.0, from the parent ion, m/z 535.5. The extraction efficiency of the method at the limit of detection was estimated as 40% (n = 10), the ion suppression as 5% (n = 10), and the limit of detection was 50 pg/ml (signal-to-noise ratio greater than 3). The selectivity of the method was verified against several endogenous and synthetic desmopressin-related peptides. The performance and the applicability of the method were tested by analysis of clinical samples after administration of desmopressin via intravenous, oral, and intranasal routes. Only after intravenous administration could desmopressin be successfully detected.     

Effects of glow discharge plasma on Cu–Co–Al-based supported catalysts for higher alcohol synthesis

The novel plasma assisted Cu–Co/γ-Al₂O₃ catalysts were prepared by incipient impregnation method for CO hydrogenation to higher alcohols and characterized by means of scanning electron microscopy (SEM), N₂ adsorption, X-ray powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) techniques. It was found that introduction of plasma significantly improved the specific surface area, dispersion of catalyst and the enrichment of active species on the surface of catalysts. Under the conditions of P = 5.0 MPa, GHSV = 6,000 h⁻¹, V(H₂)/V(CO) = 2, T = 573 K, the conversion of carbon monoxide over the plasma enhanced catalyst increased by 41.9% compared with that of the conventional sample, and the space time yield reached 337.1 g kg⁻¹ h⁻¹.     

Characterization and quantification of metallothionein isoforms by capillary electrophoresis–inductively coupled plasma–isotope-dilution mass spectrometry

In a new approach to the characterization and quantification of metallothionein isoforms an on-line isotope-dilution method in combination with the coupling of capillary electrophoresis (CE) to an inductively coupled plasma-sector field mass spectrometer (ICP-SFMS) is reported. Metallothionein (MT) isoforms are separated by CE and the elements Cu, Zn, Cd, and S are detected simultaneously by use of ICP-SFMS in the medium resolution mode. On-line isotope dilution is performed by continuous introduction of an isotopically enriched, species-unspecific spike solution after the separation step. MT from rabbit liver and a further purified MT-1 isoform were quantified by determination of sulfur, and the stoichiometric compositions of the metalloprotein complexes are characterized by determination of their sulfur-to-metal ratios.     

Dried plasma spot–based liquid chromatography–tandem mass spectrometry for the quantification of methotrexate in human plasma and its application in therapeutic drug monitoring

Methotrexate, a folic acid antitumor drug, is widely used to treat childhood acute lymphoblastic leukemia. Therapeutic drug monitoring is crucial for adjusting the dosage of methotrexate according to its plasma concentration and reducing adverse effects. Micro-sampling strategies, like dried plasma spot, is an attractive but underutilized method that has the desired features of easy collection, storage, and transport, and overcomes known hematocrit issues in dried blood spot analysis. This study describes a dried plasma spot–based liquid chromatography–tandem mass spectrometry method for quantification of methotrexate. The assay showed good linearity over 30–2000 ng/mL (R² ≥ 0.995) as well as excellent precision (0.6–9.3%) and accuracy (89.2–108.3%). Methotrexate was extracted from dried plasma spot and wet plasma samples with recoveries greater than 92.1%, and no significant matrix effect was observed. A comparison of dried plasma spot and wet plasma concentrations was assessed in 27 patients treated with methotrexate and Passing–Bablok regression coefficients showed that no significant difference between the two methods. The Bland–Altman plots showed similar agreement between the methods, indicating that the proposed dried plasma spot sampling method is an effective way to monitor the concentration of methotrexate in human plasma.     

Determination of phenazopyridine in human plasma via LC–MS and subsequent development of a pharmacokinetic model

This paper describes a new LC–MS method for the determination of phenazopyridine and the subsequent development of a pharmacokinetic model for phenazopyridine in vivo. Phenazopyridine hydrochloride is a strong analgesic used in the treatment of urinary tract infections. Although it has been used as a clinical treatment for a very long time, pharmacokinetic data and suitable methods for its determination in plasma are currently lacking. The study described in this paper used high performance liquid chromatography–mass spectrometry, HPLC–MS, to determine the plasma concentrations of phenazopyridine in human subjects after oral administration. After liquid–liquid extraction, the phenazopyridine in the plasma was analyzed on a C₁₈ column under SIM mode. A double-peak phenomenon was observed in most of the concentration–time profiles of the subjects. Although some drugs are known to cause this phenomenon, phenazopyridine has not been reported to do so. Several possible causes were analyzed in order to obtain an explanation. We proposed a two-site absorption compartment model to fit the concentration data in vivo, which has one more absorption site than the classical one-compartment model. The model describes the concentration profiles in different dose groups well and could provide an explanation for the double-peak phenomenon. The three dose groups exhibited similar model parameters and a linear pharmacokinetic process over the dose range used.     

Trace elemental analysis of automotive paints by laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS)

Paints and coatings are frequently encountered as types of materials that are submitted to forensic science laboratories as a result of trace evidence transfers. The aim of this study was to develop a method to complement the commonly used techniques in a forensic laboratory in order to better characterize these samples for forensic purposes. A laser ablation method has been used to simultaneously sample several layers directly prior to introduction into an inductively coupled plasma-mass spectrometer for the detection and quantification of the trace metals present in the layer(s). Time-resolved analysis plots displaying the elemental response and quantification of selected metals are compared to associate/discriminate paint samples. Matrix-matched standards were successfully incorporated into the analysis scheme for quantification of lead in the solid paint samples. Preparation of new matrix-matched standards for quantification of additional elements developed for this study are also presented. A sample set of eighteen (18) survey automotive paint samples have been analyzed with the developed method in order to determine the utility of LA-ICP-MS for trace element analysis of paints.     

Geographic characterization of Greek wine by inductively coupled plasma–mass spectrometry macroelemental analysis

Abstract

Studying wine mineral profile has been proven as a valuable tool in geographical origin discrimination and authenticity for both producers and consumers. Adulteration of wines, in terms of geographical origin or variety, is considered a major topic of extensive research. Traceability and authenticity of wines have been previously studied on the basis of typical mineral element patterns by means of chemometric methods. In this context, analytical methods were developed for the determination of mineral elements in wines by inductively coupled plasma–mass spectrometry. This study aimed at classifying selected varietal Greek wines from various regions by employing instrumental analysis. Preliminary data of wine mineral content enabled for the classification of samples according to geographical origin and variety. However, further work is required in order to draw more valid conclusions and to obtain a detailed map of the mineral element content of Greek wines according to their geographical origin and/or variety.     

Determination of lesinurad in rat plasma by a UHPLC–MS/MS assay

Lesinurad is an oral inhibitor of urate-anion exchanger transporter 1 and has been approved by the US Food and Drug Administration for combination therapy with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with refractory gout. In the present study, a sensitive and specific ultra high-performance liquid chromatography with tandem mass spectrometry assay was established and verified for the determination of lesinurad in rat plasma and was described in details for the first time. Chromatographic separation of lesinurad and diazepam (internal standard, IS) was performed on a Rapid Resolution HT C18 column (3.0 × 100 mm, 1.8 µm) using methanol–water (70:30, v/v) as the mobile phase at a flow rate of 0.3 mL/min. Lesinurad and IS were extracted from plasma by liquid–liquid extraction using ethyl acetate. The mass spectrometric detection was carried out using an electrospray ionization source in positive mode. Multiple reaction monitoring was used for quantification of the precursor to product ion at m/z 405.6 → 220.9 for lesinurad and m/z 285.1 → 192.8 for IS. The assay was well validated for selectivity, accuracy, precision, recovery, linearity, matrix effects, and stability. The verified method was applied to obtain the pharmacokinetic parameters and concentration–time profiles for lesinurad after oral/intravenous administration in rats. The study might provide an important reference and a necessary complement for the qualitative and quantitative evaluation of lesinurad.     

Quantification of clomiphene metabolite isomers in human plasma by rapid-resolution liquid chromatography–electrospray ionization–tandem mass spectrometry

Since the 1960s, clomiphene citrate is used for ovulation induction. Since nonresponse to clomiphene therapy is still not well understood, interindividual variability of clomiphene metabolism has been considered to be a plausible explanation. Therefore, a comprehensive, rapid, sensitive, and specific analytical method for the quantification of (E)- and (Z)-isomers of clomiphene and their putative N-desethyl, N,N-didesethyl, 4-hydroxy, and 4-hydroxy-N-desethyl metabolites, and the N-oxides in human plasma has been newly developed, using HPLC-tandem mass spectrometry and stable isotope-labeled internal standards. All standards other than the parent drug were synthesized in our laboratory. Following protein precipitation analytes were separated on a ZORBAX Eclipse plus C18 1.8 μm column with a gradient of 0.1% formic acid in water and 0.1% formic acid in acetonitrile and detected on a triple quadrupole mass spectrometer with positive electrospray ionization in the multiple reaction monitoring mode. Lower limit of quantification for metabolites ranged from 0.06 ng/mL for clomiphene-N-oxides to 0.3 ng/mL for (E)-N-desethylclomiphene. The assay was validated according to FDA guidelines. Plasma levels of clomiphene and its metabolites were measured in two women after single-dose treatment with clomiphene.     

Physical and analytical characteristics of an atmospheric pressure argon–helium radiofrequency capacitively coupled plasma

A very low power radiofrequency capacitively coupled plasma (13.56 MHz, 5–70 W), was generated in our laboratory on a sharp Kanthal tip without any counter electrode, as an intrinsic part of RLC series resonant circuit. Physical characteristics of this plasma obtained in Ar–He mixture, were studied as function of observation height or gas mixture composition. The excitation temperature of Ar (1500–2100 K), He (3000–3500 K) and H (2500–3200 K), the rotational temperature of the OH band (1300–2900 K), the electron temperature (5500–6500 K) and the electron number density (8 · 10¹³–2 · 10¹⁴ cm^− 3) were determined. The evolution of several atomic emission lines or molecular bands was studied in order to investigate the fundamental processes that take place in such plasma. From the point of view of analytical applications it was found that the optimum conditions of excitation (most intense emission lines and lowest detection limits) are met for a 42% He in the gas mixture and an observation height of 1 mm above the electrode. The optimum atomic emission analysis parameters were established for 7 elements (Na, Li, Ca, K, Cd, Zn and Hg) using pneumatically nebulized liquid solutions. It was found that the presence of He in the plasmogenic gas has an enhancing effect on the emission intensities and detection limits.     

A spectroscopic study of laser-induced tin–lead plasma: Transition probabilities for spectral lines of Sn I

In this paper, we present transition probabilities for 97 spectral lines of Sn I, corresponding to transitions n(n = 6,7,8)s → 5p², n(n = 5,6,7)d → 5p², 5p³ → 5p², n(n = 7)p → 6s, determined by measuring the intensities of the emission lines of a Laser-induced breakdown (emission) spectrometry (LIBS). The optical emission spectroscopy from a laser-induced plasma generated by a 10 640 Å radiation, with an irradiance of 1.4 × 10¹⁰ Wcm^− 2 on an Sn–Pb alloy (an Sn content of approximately 20%), in vacuum, was recorded at 0.8 µs, and analysed between 1900 and 7000 Å. The population-level distribution and corresponding temperature were obtained using Boltzmann plots. The electron density of the plasma was determined using well-known Stark broadening parameters of spectral lines. The plasma under study had an electron temperature of 13,200 K and an electron number density of 2 × 10¹⁶ cm^− 3. The experimental relative transition probabilities were put on an absolute scale using the branching ratio method to calculate Sn I multiplet transition probabilities from available radiative lifetime data of their upper states and plotting the Sn I emission spectrum lines on a Boltzmann plot assuming local thermodynamic equilibrium (LTE) to be valid and following Boltzmann's law. The LTE conditions and plasma homogeneity have been checked. Special attention was paid to the possible self-absorption of the different transitions. The experimental results obtained have been compared with the experimental values given by other authors.