Dual separation mode for simultaneous determination of antihypertensive drug combinations by high-performance liquid chromatography

A simple, reproducible and efficient dual separation mode high performance liquid chromatographic (HPLC) method was developed for simultaneous determination of antihypertensive drug combinations including; hydrochlorothiazide (HCTZ), valsartan (VAL), amiloride (AML) and captopril (CAP). The newly developed Platinum™ column, which provides a dual-mode separation with its polar and non-polar sites, was used for rapid separation of these co-administered drugs. Good resolution was obtained when Platinum™ column was used compared with C₁₈ column. Additionally, simple isocratic mode with mobile phase containing methanol and 0.02 mole L⁻¹ phosphate buffer adjusted to pH 3.0 (45:55, v/v) was used for separation. The flow rate was 0.5 mL min⁻¹ and effluent was monitored at 270 nm. All the investigated drugs were completely separated within less than 6 min. The linearity range obtained for the developed HPLC method was 0.5-100 μg mL⁻¹ with detection limits of 0.13-1.2 μg mL⁻¹ for all the studied drugs. The method was validated in accordance with the requirements of ICH guidelines and shown to be suitable for intended applications. The method was successfully used for determination of the studied drugs in pure form and pharmaceutical dosage forms without prior need for separation. The method is valuable for quality control laboratories for simultaneous determination of these co-administered antihypertensive drugs in binary, ternary and quaternary mixtures.     

Multi-element preconcentration of heavy metal ions from aqueous solution by APDC impregnated activated carbon

Ammonium pyrrolidinedithiocarbamate impregnated activated carbon (APDC-AC) has been used for the preconcentration of Cd(II), Cu(II), Ni(II), and Zn(II) from aqueous solution by column solid phase extraction (SPE) technique. Trace metal ions in aqueous solution were quantitatively sorbed onto APDC-AC packed in a SPE column at pH 5.0 with a flow rate of 1.0 mL min⁻¹. The sorbed metals were eluted with 1 M nitric acid in acetone solution at a flow rate of 0.6 mL min⁻¹ and analyzed by flame atomic absorption spectrometry. The effects of sample volume, amount of APDC-AC, volume of eluent and ionic strength of working solution on metal ion recovery have been investigated. The present methodology gave recoveries from 90 to 106% and R.S.D. from 0.6 to 5.5%.     

Single-run ion chromatographic separation of inorganic and low-molecular-mass organic anions under isocratic elution: Application to environmental samples

For the isocratic ion chromatography (IC) separation of low-molecular-mass organic acids and inorganic anions three different anion-exchange columns were studied: IonPac AS14 (9 μm particle size), Allsep A-2 (7 μm particle size), and IC SI-50 4E (5 μm particle size). A complete baseline separation for all analyzed anions (i.e., F⁻, acetate, formate, Cl⁻, NO₂⁻, Br⁻, NO₃⁻, HPO₄²⁻ and SO₄²⁻) in one analytical cycle of shorter than 17 min was achieved on the IC SI-50 4E column, using an eluent mixture of 3.2 mM Na₂CO₃ and 1.0 mM NaHCO₃ with a flow rate of 1.0 mL min⁻¹. On the IonPac AS14 column, it was possible to separate acetate from inorganic anions in one run (i.e., less than 9 min), but not formate, under the following conditions: 3.5 mM Na₂CO₃ plus 1.0 mM NaHCO₃ with a flow rate of 1.2 mL min⁻¹. Therefore, it was necessary to adapt a second run with a 2.0 mM Na₂B₄O₇ solution as an eluent under a flow rate of 0.8 mL min⁻¹ for the separation of organic ions, which considerably enlarged the analysis time. For the Allsep A-2 column, using an eluent mixture of 1.2 mM Na₂CO₃ plus 1.5 mM NaHCO₃ with a flow rate of 1.6 mL min⁻¹, it was possible to separate almost all anions in one run within 25 min, except the fluoride-acetate critical pair. A Certified Multianion Standard Solution PRIMUS for IC was used for the validation of the analytical methods. The lowest RSDs (less than 1%) and the best LODs (0.02, 0.2, 0.16, 0.11, 0.06, 0.05, 0.04, 0.14 and 0.09 mg L⁻¹ for F⁻, Ac⁻, For⁻, Cl⁻, NO₂⁻, Br⁻, NO₃⁻, HPO₄²⁻ and SO₄²⁻, respectively) were achieved using the IC SI-50 4E column. This column was applied for the separation of concerned ions in environmental precipitation samples such as snow, hail and rainwater.     

Separation of zinc compounds by sequential metal vapor elution analysis with atomic absorption detection

The separation of zinc compounds, containing zinc chloride, nitrate, and sulfate, at low concentrations by sequential metal vapor elution analysis (SMVEA) with argon carrier gas was reported. A molybdenum column, inserted with a tungsten wire, was developed for the separation of zinc compounds by SMVEA. The optimum separation conditions were a vaporization temperature of 1370 K, a column temperature of 1350 K, and a carrier gas flow rate of 2.5 mL min⁻¹. Under the optimized experimental conditions, the zinc compounds could be roughly separated by SMVEA, although a part of peak profiles overlapped. The number of theoretical plates was 36 for ZnCl₂, 62 for Zn(NO₃)₂, and 80 for ZnSO₄ in the SMVEA column. The present SMVEA system may be able to be applied widely to various analytical instruments.     

Development and validation of a rapid HPLC method for the determination of five banned fat-soluble colorants in spices using a narrow-bore monolithic column

This work reports a fast and simple liquid chromatographic method for the simultaneous determination of five banned fat-soluble synthetic colorants, namely Sudan I-IV and Para-Red, in spice samples. The analytes were successfully separated isocratically in less than 5 min on the new narrow bore monolithic column, FastGradient^® Chromolith (50 mm × 2.0 mm i.d.) using a mobile phase of 0.1% (v/v) HCOOH/acetonitrile (35/65%, v/v) at a flow rate of 1.5 mL min⁻¹. All colorants were detected at 506 nm. The main parameters (mobile phase composition, flow rate, injection volume) affecting the separation were studied. The proposed method was thoroughly validated in terms of linearity, LODs, precision and accuracy. The method was applied to the determination of the studied azo-dyes in various spices (paprika, chilli and mixed spice powders) after ultrasound-assisted extraction. Satisfactory recoveries, ranging from 92% to 109% were obtained.     

Evaluation of polychlorotrifluoroethylene as sorbent material for on-line solid phase extraction systems: determination of copper and lead by flame atomic absorption spectrometry in water samples

Polychlorotrifluoroethylene (PCTFE) in the form of beads was applied, as packing material for flow injection on-line column preconcentration and separation systems coupled with flame atomic absorption spectrometry (FAAS). Its performance characteristics were evaluated for trace copper determination in environmental samples. The on-line formed complex of metal with diethyldithiophosphate (DDPA) was sorbed on the PCTFE surface. Isobutyl methyl ketone (IBMK) at a flow rate of 2.8 mL min⁻¹ was used to elute the analyte complex directly into the nebulizer-burner system of spectrophotometer. The proposed sorbent material reveal, excellent chemical and mechanical resistance, fast adsorption kinetics permitting the use of high sample flow rates up to 15 mL min⁻¹ without loss of retention efficiency. For copper determination, with 90 s preconcentration time the sample frequency was 30 h⁻¹, the enhancement factor was 250, which could be further improved by increasing the loading (preconcentration) time. The detection limit (3s) was c_L = 0.07 μg L⁻¹, and the precision (R.S.D.) was 1.8%, at the 2.0 μg L⁻¹ Cu(II) level. For lead determination, the detection limit was c_L = 2.7 μg L⁻¹, and the precision (R.S.D.) 2.2%, at the 40.0 μg L⁻¹ Pb(II) level. The accuracy of the developed method was evaluated by analyzing certified reference materials and by recovery measurements on spiked natural water samples.     

Development and validation of a high-throughput high-performance liquid chromatographic assay for the determination of caffeine in food samples using a monolithic column

The present study reports the development and validation of a high-throughput high-performance liquid chromatographic (HPLC) assay for the determination of caffeine in food samples. The analyte was separated rapidly from sample matrix using a short monolithic column (50 mm × 4.6 mm i.d.). The flow rate was 3.0 mL min⁻¹, while the mobile phase consisted of ACN/water (10:90, v/v). Caffeine was detected directly at 274 nm. Under the optimal HPLC conditions, the sampling rate was 60 h⁻¹. The assay was validated for linearity, LOD and LOQ, precision, selectivity and ruggedness. The case of external calibration versus standard addition for the analysis of real samples was also examined. The proposed assay was applied to the analysis of beverages and coffee samples.     

Determination of dye precursors in hair coloring products by liquid chromatography with electrochemical detection

The simultaneous determination of seven aminophenols, resorcinol and p-phenylenediamine in hair coloring products was performed by liquid chromatography (HPLC) with amperometric detection (ED). The aminophenols were separated on a ODS C18 reversed-phase column by isocratic elution with a mobile phase based on 0.1 M acetate buffer pH 4.5-methanol (90:10%, v/v) at a flow rate 0.8 mL min⁻¹. The limit of detection (S/N = 3) for the aminophenols was in the 15-40 pg (injected mass) range at an applied potential of 0.950 V versus Ag/AgCl. Peak heights for the aminophenols and the two others compounds were found to be linearly related to the amount injected, from 0.3 to 300 ng (r > 0.994-0.999).The relative standard deviation (R.S.D., n = 10) for 1 ng injected was comprised in the range from 2.5 to 6.2%, depending on the aminophenol tested. The present method minimizes troublesome and time-consuming pretreatment procedures and it was applied to the determination of aminophenols, resorcinol and phenylenediamine in hair coloring formulations.     

Development and validation of an ion pair HPLC method for gemcitabine and 2′,2′-difluoro-2′-deoxyuridine determination

A reverse phase HPLC method based on ion-pair formation was set up for the simultaneous determination of gemcitabine and its metabolite 2′,2′-difluoro-2′-deoxyuridine (dFdU) in plasma samples obtained from cancer patients. The separation was performed on a μBondapack C₁₈ (300 mm × 3.9 mm i.d., 10 μm particle size) column at room temperature. The mobile phase, 5 mM pentane-1-sulfonic acid pH 3.1/methanol (96:4), was pumped at a flow rate of 1.5 mL min⁻¹. Gemcitabine and dFdU eluted in less than 16 min. Linearity, sensitivity, and reproducibility studies, which actual values met the demands for bioanalytical assays, validated the method. This assay provided pharmacokinetic data from patients treated with intravenous gemcitabine.     

Development of high performance liquid chromatography method for lacidipine in rabbit serum: Application to pharmacokinetic study

A simple and sensitive high performance liquid chromatographic (HPLC) method for quantification of lacidipine (LCDP) in rabbit serum was developed and validated. LCDP and internal standard (IS), felodipine were extracted into n-hexane and dichloromethane (70:30) solvent system and separated using an isocratic mobile phase, on an Inertsil C18 column. The effluent was monitored by UV detector at 240 nm and at a flow rate of 1.0 mL min⁻¹. The linearity range of proposed method was 1-500 ng mL⁻¹. The intra-day and inter-day coefficient of variation and percent error values of the assay method were less than 15% and mean recovery was more than 94 and 95% for LCDP and IS, respectively and the method was found to be precise, accurate, and specific during the study. The method was successfully applied for pharmacokinetic study of lacidipine after application of LCDP microemulsion gel in rabbits.     

Determination of pesticides fenoxycarb and permethrin by sequential injection chromatography using miniaturized monolithic column

Sequential injection chromatography system equipped with miniaturized 10 mm monolithic column was used for fast simultaneous determination of two pesticides—fenoxycarb (FC) and permethrin (PM). The system was composed of a commercial sequential injection analysis (SIA) system (FIAlab^® 3000, 6-port selection valve and 5.0 mL syringe pump), commercially available column Chromolith™ RP-18e (10 mm × 4.6 mm i.d.) (Merck^®, Germany) and CCD UV-vis detector (USB 2000, Ocean-optics) with 1.0 cm Z-flow cell, absorbance was monitored at 225 nm. The mobile phase used for analysis was acetonitrile/water (60:40, v/v), flow rates were 0.6 mL min⁻¹ for elution of fenoxycarb and 1.2 mL min⁻¹ for elution of permethrin. For each analysis 4.8 mL of mobile phase was used. The chromatographic resolution between both compounds was >8 and analysis time was <6.5 min under the optimal conditions. Limits of detection were determined at 2.0 μg mL⁻¹ for fenoxycarb and 1.0 μg mL⁻¹ for permethrin. Samples were prepared by diluting with mobile phase and injected volume was 10 μL for each analysis. Developed method was applied to analysis of both pesticides in veterinary pharmaceutical foams and sprays ARPALIT^® Neo (Aveflor, Czech Republic). SIC method was compared with validated method (HPLC, reverse phase 100 mm monolithic column, gradient elution).     

Modified mesoporous silica materials for on-line separation and preconcentration of hexavalent chromium using a microcolumn coupled with flame atomic absorption spectrometry

A modified SBA-15 mesoporous silica material NH₂-SBA-15 was synthesized successfully by grafting γ-aminopropyl-triethoxysilane. The material was characterized using transmission electron microscopy (TEM) and Fourier transform infrared/Raman (FT-IR/Raman) spectroscopy, and used for the first time in a flow injection on-line solid phase extraction (SPE) coupled with flame atomic absorption spectrometry (FAAS) to detect trace Cr (VI). Effective sorption of Cr (VI) was achieved at pH 2.0 with no interference from Cr (III) and other ions and 0.5 mol L⁻¹ NH₃·H₂O solution was found optimal for the complete elution of Cr (VI). An enrichment factor of 44 and was achieved under optimized experimental conditions at a sample loading of 2.0 mL min⁻¹ sample loading (300 s) and an elution flow rate of 2.0 mL min⁻¹ (24 s). The precision of the 11 replicate Cr (VI) measurements was 2.1% at the 100 μg L⁻¹ level with a detection limit of 0.2 μg L⁻¹ (3 s, n = 10) using the FAAS. The developed method was successfully applied to trace chromium determination in waste water. The accuracy was validated using a certified reference material of riverine water (GBW08607).     

Development of high performance liquid chromatography method for buspirone in rabbit serum: Application to pharmacokinetic study

A simple and sensitive high performance liquid chromatographic (HPLC) method for quantification of buspirone (BUSP) in rabbit serum was developed and validated. BUSP and internal standard (IS), diltiazem hydrochloride were extracted into dichloromethane and separated using an isocratic mobile phase, on a Kromasil C₈ column. The eluent was monitored by UV detector at 235 nm and at a flow rate of 1.0 mL min⁻¹. The linearity range of proposed method was 1-3000 ng mL⁻¹. The intra-day and inter-day coefficient of variation and percent error values of the assay method were less than 15% and mean recovery was more than 97 and 96% for BUSP and IS, respectively. The method was found to be precise, accurate, and specific during the study. The method was successfully applied for pharmacokinetic study of buspirone after application of reservoir based transdermal therapeutic system of BUSP to rabbits.     

Non-chromatographic determination of ultratraces of V(V) and V(IV) based on a double column solid phase extraction flow injection system coupled to electrothermal atomic absorption spectrometry

In this work, a non-chromatographic procedure for the on-line determination of ultratraces of V(V) and V(IV) is presented. The method involves a solid phase extraction-flow injection system coupled to electrothermal atomic absorption spectrometry (SPE-FI-ETAAS). The system holds two microcolumns (MC) set in parallel and filled with lab-made mesoporous silica functionalized with 3-aminopropyltriethoxy silane (APS) and mesoporous silica MCM-41, respectively. The pre-concentration of V(V) is performed by sorption onto the first MC (C1) filled with APS at pH 3, whilst that of V(IV) is performed by sorption onto the second column (C2) filled with mesoporous silica MCM-41 at pH 5. Aqueous samples containing both analytes are loaded and, after pre-concentration (pre-concentration factor PCF = 10, sorption flow rate = 1 mL min⁻¹, sorption time = 10 min), they are eluted in separate vessels with hydroxylammonium chloride (HC) 0.1 mol L⁻¹ in HCl 0.5 mol L⁻¹ (elution volume = 1 mL, elution flow rate = 0.5 mL min⁻¹). Afterwards, both analytes are determined through ETAAS with graphite furnace. Under optimized conditions, the main analytical figures of merit for V(V) and V(IV) are, respectively: detection limits (3 s): 0.5 and 0.6 μg L⁻¹, linear range: 2-100 μg L⁻¹ (both analytes), sensitivity: 0.015 and 0.013 μg⁻¹ L and sample throughput: 6 h⁻¹ (both analytes). Recoveries of both species were assayed in different water samples. Validation was performed through certified reference materials for ultratraces of total vanadium in river water.     

A rapid, acetonitrile-free, HPLC method for determination of melamine in infant formula

A simple, precise, accurate and validated, acetonitrile-free, reverse phase high performance liquid chromatography (HPLC) method is developed for the determination of melamine in dry and liquid infant formula. The separation is performed on a Kromasil C18 column (150 mm × 3.2 mm I.D., 5 μm particle size) at room temperature. The mobile phase (0.1% TFA/methanol 90:10) is pumped at a flow rate of 0.3 mL min⁻¹ with detection at 240 nm. Melamine elutes at 3.7 min. A linear response (r > 0.999) is observed for samples ranging from 1.0 to 80 μg mL⁻¹. The method provides recoveries of 97.2-101.2% in the concentration range of 5-40 μg mL⁻¹, intra- and inter-day variation in <1.0% R.S.D. The limit of detection (LOD) and limit of quantification (LOQ) values are 0.1 μg mL⁻¹ and 0.2 μg mL⁻¹, respectively.     

Simultaneous liquid chromatographic determination of metals and organic compounds in pharmaceutical and food-supplement formulations using evaporative light scattering detection

A novel method for the non-derivatization liquid chromatographic determination of metals (potassium, aluminium, calcium and magnesium) and organic compounds (ascorbate and aspartate) was developed and validated based on evaporative light scattering detection (ELSD). Separation of calcium, magnesium and aluminium was achieved by the cation exchange column Dionex CS-14 and an aqueous TFA mobile phase according to the following time program: 0-6 min TFA 0.96 mL L⁻¹, 6-7 min linear gradient from TFA 0.96-6.4 mL L⁻¹. Separation of potassium, magnesium and aspartate was achieved by the lipophilic C₁₈ Waters Spherisorb column and isocratic aqueous 0.2 mL L⁻¹ TFA mobile phase. Separation of sodium, magnesium, ascorbate and citrate was also achieved by the C₁₈ analytical column, according to the following elution program: 0-2.5 min aqueous nonafluoropentanoic acid (NFPA) 0.5 mL L⁻¹; 2.5-3.5 min linear gradient from 0.5 mL L⁻¹ NFPA to 1.0 mL L⁻¹ TFA. In all cases, evaporation temperature was 70 °C, pressure of the nebulizing gas (nitrogen) 3.5 bar, gain 11 and the flow rate 1.0 mL min⁻¹. Resolution among calcium and magnesium was 1.8, while for all other separations was ≥3.2. Double logarithmic calibration curves were obtained within various ranges from 3-24 to 34-132 μg mL⁻¹, and with good correlation (r > 0.996). Asymmetry factor ranged from 0.9 to 1.9 and limit of detection from 1.3 (magnesium) to 17 μg mL⁻¹ (ascorbate).The developed method was applied for the assay of potassium, magnesium, calcium, aluminium, aspartate and ascorbate in pharmaceuticals and food-supplements. The accuracy of the method was evaluated using spiked samples (%recovery 95-105%, %R.S.D. < 2) and the absence of constant or proportional errors was confirmed by dilution experiments.     

Liquid chromatographic determination of sitagliptin either alone or in ternary mixture with metformin and sitagliptin degradation product

Two reversed-phase liquid chromatographic (RP-LC) methods have been developed for the determination of sitagliptin phosphate monohydrate (STG). The first method comprised the determination of STG alone in bulk and plasma; and in its pharmaceutical preparation. This method was based on isocratic elution of STG using a mobile phase consisting of potassium dihydrogen phosphate buffer pH (7.8)-acetonitrile (70:30, v/v) at a flow rate of 1 mL min⁻¹ with flourometric detection. The flourometric detector was operated at 267 nm for excitation and 575 nm for emission. In the second method, the simultaneous determination of STG and metformin (MET) in the presence of sitagliptin alkaline degradation product (SDP) has been developed. In this method, the ternary mixture of STG, MET and SDP was separated using a mobile phase consisting of potassium dihydrogen phosphate buffer pH (4.6)-acetonitrile-methanol (30:50:20, v/v/v) at a flow rate of 1 mL min⁻¹ with UV detection at 220 nm. Chromatographic separation in the two methods was achieved on a Symmetry^® Waters C18 column (150 mm × 4.6 mm, 5 μm). Linearity, accuracy and precision were found to be acceptable over the concentration ranges of 0.25-200 μg mL⁻¹ for STG with the first method and 5-160 μg mL⁻¹, 25-800 μg mL⁻¹ for STG and MET, respectively with the second method. The optimized methods were validated and proved to be specific, robust and accurate for the quality control of the cited drugs in pharmaceutical preparations.     

Simultaneous determination of antioxidants, preservatives and sweetener additives in food and cosmetics by flow injection analysis coupled to a monolithic column

Today it is common to find samples with various additives from several families. This is the case of sweeteners, preservatives and antioxidants. We have selected a set of additives broadly used in foods and cosmetics with an ample variety of polarities, namely: aspartame (AS), acesulfame (AK)/saccharin (SA), metylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), propylgallate (PG) and butylhydroxyanysole (BA). The monolithic column used as separative system is a 5 mm commercial precolumn of silica C₁₈ coupled to a flow injection manifold working with a peristaltic pump. The mixture was separated in only 400 s with resolution factors greater than 1.1 in all cases. To achieve the separation in the FIA system we used two carriers: first, a mixture of ACN/water buffered with 10 mM pH 6.0 phosphate buffer and second, a methanol:water mixture to improve the carrier strength and speed up the more apolar analytes at 3.5 mL min⁻¹. Detection is accomplished by means of a diode array spectrometer at the respective wavelength of each compound. The comparison of the analytical parameters obtained for this procedure with a standard HPLC method validates our new method, obtaining a method that is quick, with high repeatability and reproducibility and with good resolution between analytes. We have successfully applied the method to real food and cosmetics samples.     

Determination of tadalafil in pharmaceutical preparation by HPLC using monolithic silica column

The simple, reliable and reproducible HPLC and extraction methods were developed for the analysis of tadalafil in pharmaceutical preparation. The column used was monolithic silica column, Chromolith Performance RP-18e (100 mm × 4.6 mm, i.d.). The mobile phase used was phosphate buffer (100 mM, pH 3.0)-acetonitrile (80:20, v/v) at the flow rate of 5 mL min⁻¹ with UV detection at 230 nm at ambient temperature. Extraction of tadalafil from tablet was carried out using methanol. Linearity was observed in the concentration range from 100 to 5000 ng mL⁻¹ for tadalafil with a correlation coefficient (R²) 0.9999 and 100 ng mL⁻¹ as the limit of detection. The values of linearity range, correlation coefficient (R²) and limit of detection were 50-5000 ng mL⁻¹, 0.9999-50 ng mL⁻¹, respectively for sildenafil. Parameters of validation prove the precision of the method and its applicability for the determination of tadalafil in pharmaceutical tablet formulation. The method is suitable for high throughput analysis of the drug.     

Comparison of two lab-made spray chambers based on MSIS™ for simultaneous metal determination using vapor generation-inductively coupled plasma optical emission spectroscopy

The objective of this study is to evaluate the performance of two lab-made systems based on the Multimode Introduction System (MSIS™) and the modified MSIS™, to generate and introduce vapors of Ag, Cu, Cd, Cu, Ni, Sn, Zn, and also Au in the ICP torch. An univariate procedure was used to select the optimized working conditions (Ar flow, sample, reductant and waste flows, and reagent concentrations). Optimum conditions for working with modified MSIS were: nitric acid concentration 0.35 M, 8-hydroxyquinoline concentration: 40 mg L⁻¹, sodium borohydride concentration: 1.75% (w/v) + 0.4% (w/v) NaOH, argon purge flow to sweep the vapors to the torch: 1.2 L min⁻¹, sample flow and sodium borohydride flows: 2.3 L min⁻¹; waste flow: 7.7 mL min⁻¹. For the optimum working conditions for lab-made MSIS in dual mode the concentration of 8-hydroxyquinoline was 225 mg L⁻¹, the Ar purge flow was 0.75 L min⁻¹, and the conventional nebulization flow was 2.3 L min⁻¹. The sensitivity obtained was higher using the lab-made MSIS than using the lab-made modified MSIS or a forced outlet gas–liquid separator. The limits of detection were better for Au, Cd, Sn than those obtained using conventional nebulization; the measurements were precise (RSDs ≤ 5% in dual mode) and a good accuracy was obtained in the determination of Cd, Cu, Ni and Zn in a wastewater reference material using aqueous calibration and the lab-made MSIS in dual mode.