Determination of ruthenium originating from the investigational anti-cancer drug NAMI-A in human plasma ultrafiltrate, plasma, and urine by inductively coupled plasma mass spectrometry

We present a highly sensitive, rapid method for the determination of ruthenium originating from the investigational anti-cancer drug NAMI-A in human plasma ultrafiltrate, plasma, and urine. The method is based on the quantification of ruthenium by inductively coupled plasma mass spectrometry and allows quantification of 30 ng L(-1) ruthenium in plasma ultrafiltrate and urine, and 75 ng L(-1) ruthenium in human plasma, in 150 microL of matrix. The sample pretreatment procedure is straightforward and only involves dilution with appropriate diluents. The performance of the method, in terms of accuracy and precision, fulfilled the most recent FDA guidelines for bioanalytical method validation. Validated ranges of quantification were 30.0 to 1 x 10(4) ng L(-1) for ruthenium in plasma ultrafiltrate and urine and 75.0 to 1 x 10(4) ng L(-1) for ruthenium in plasma. The applicability of the method and its superiority to atomic-absorption spectrometry were demonstrated in two patients who were treated with intravenous NAMI-A in a phase I trial. The assay is now successfully used to support pharmacokinetic studies in cancer patients treated with NAMI-A.     

Determination of glyphosate and phosphate in water by ion chromatography--inductively coupled plasma mass spectrometry detection

Quantitative determination of trace glyphosate and phosphate in waters was achieved by coupling ion chromatography (IC) separation with inductively coupled plasma mass spectrometry (ICP-MS) detection. The separation of glyphosate and phosphate on a polymer anion-exchange column (Dionex IonPac AS16, 4.0 mm x 250 mm) was obtained by eluting them with 20 mM citric acid at 0.50 mL min(-1), and the analytes were detected directly and selectively by ICP-MS at m/z = 31. Parameters affecting their chromatographic behaviors and ICP-MS characteristics were systematically examined. Based on a 500-microL sample injection volume, the detection limits were 0.7 microgL(-1) for both glyphosate and phosphate, and the calibrations were linear up to 400 microgL(-1). Polyphosphates, aminomethylphosphonic acid (the major metabolite of glyphosate), non-polar and other polar phosphorus-containing pesticides showed different chromatographic behaviors from the analytes of interest and therefore did not interference. The determination was also interference free from the matrix anions (nitrate, nitrite, sulphate, chloride, etc.) and metallic ions. The analysis of certified reference material, drinking water, reservoir water and Newater yielded satisfactory results with spiked recoveries of 97.1-107.0% and relative standard deviations of < or = 7.4% (n = 3). Compared to other reported methods for glyphosate and phosphate, the developed IC-ICP-MS method is sensitive and simple, and does not require any chemical derivatization, sample preconcentration and mobile phase conductivity suppression.     

Development of water-phase derivatization followed by solid-phase microextraction and gas chromatography/mass spectrometry for fast determination of valproic acid in human plasma

In this study, a simple, rapid, and sensitive method was developed and validated for the quantification of valproic acid (VPA), an antiepileptic drug, in human plasma, which was based on water-phase derivatization followed by headspace solid-phase microextraction (HS-SPME) and gas chromatography/mass spectrometry (GC/MS). In the proposed method, VPA in plasma was rapidly derivatized with a mixture of isobutyl chloroformate, ethanol and pyridine under mild conditions (room temperature, aqueous medium), and the VPA ethyl ester formed was headspace-extracted and simultaneously concentrated using the SPME technique. Finally, the analyte extracted on SPME fiber was analyzed by GC/MS. The experimental parameters and method validations were studied. The optimal conditions were obtained: PDMS fiber, stirring rate of 1100 rpm, sample temperature of 80 degrees C, extraction time of 20 min, NaCl concentration of 30%. The proposed method had a limit of quantification (0.3 microg/mL), good recovery (89-97%) and precision (RSD value less than 10%). Because the proposed method combined a rapid water-phase derivatization with a fast, simple and solvent-free sample extraction and concentration technique of SPME, the sample preparation time was less than 25 min. This much shortens the whole analysis time of VPA in plasma. The validated method has been successfully used to analyze VPA in human plasma samples for application in pharmacokinetic studies. All these results show that water-phase derivatization followed by HS-SPME and GC/MS is an alternative and powerful method for fast determination of VPA in biological fluids.     

Ultratrace-level radium-226 determination in seawater samples by isotope dilution inductively coupled plasma mass spectrometry

An improved and novel sample preparation method for ²²⁶Ra determination in liquid samples by isotope dilution inductively coupled plasma sector field mass spectrometry using laboratory-prepared ²²⁸Ra tracer has been developed. The procedure involves a selective preconcentration achieved by applying laboratory-prepared MnO₂ resin followed by cation exchange chromatographic separation. In order to completely eliminate possible molecular interferences, medium mass resolution (R = 4,000) combined with chemical separation was found to be a good compromise that enhanced the reliability of the method. The detection limit of 0.084 fg g⁻¹ (3.1 mBq kg⁻¹) achieved is comparable to that of the emanation method or alpha spectrometry and is suitable for low-level environmental measurements. The chemical recovery of the sample preparation method ranged from 72 to 94%. The proposed method enables a rapid, accurate and less labor-intensive approach to routine environmental ²²⁶Ra determination than the radioanalytical techniques conventionally applied.     

Determination of iodine and bromine in plasma and urine by inductively coupled plasma mass spectrometry

The simultaneous determination of iodine and bromine in plasma and urine by inductively coupled plasma mass spectrometry, using a Nermag prototype instrument, is described. The sample preparation involves only a 10-fold dilution with a diluent containing europium as an internal standard followed by direct nebulisation in the plasma. The iodine, bromine and europium ions are measured at m/z = 127, 79, and 153, respectively. The sensitivity of the method, with detection limits of 1.6 and 52 micrograms l-1 for iodine and bromine, respectively, is satisfactory for clinical applications. The calibration graphs were linear over the ranges 0-400 micrograms l-1 and 0-40 mg l-1 for iodine and bromine, respectively, which are wide enough for most assays. The recoveries were close to 100% with coefficients of variation of less than 3%. The within-day and between-day reproducibility was about 5%. The concentrations of iodine and bromine in the plasma of 26 healthy individuals were 58 +/- 12 micrograms l-1 and 4.1 +/- 0.9 mg l-1, respectively. The amounts of iodine and bromine eliminated in urine were 94 +/- 97 micrograms per 24 h (range 27-403 micrograms per 24 h) and 3.6 +/- 1.7 mg per 24 h, respectively. These results are in agreement with reported values.     

Development and validation of an inductively coupled plasma mass spectrometry method for quantification of levothyroxine in dissolution studies

A simple, sensitive and reproducible inductively coupled plasma mass spectrometry (ICP-MS) method for the direct determination of levothyroxine (T4), based on the analysis of iodide content, in aqueous media was developed. The sample preparation consisted of addition of antimony, as the internal standard, and dilution with a 0.5% ammonia solution. The analytes were quantified at m/z 126.90 and 120.90 for iodide and antimony, respectively. The assay was linear in the concentration range of 0.1-50 ng/mL for iodide and 0.3-100 ng/mL for T4. The method was precise and accurate with lower limits of quantification (LLOQs) of 0.1 ng/mL for iodide and 0.3 ng/mL for T4. The inter-day accuracy was >94% for both analytes and the coefficient of variation (%CV) was less than 5%. The method has successfully been used for dissolution studies of T4 formulations and holds immense promise as a simple, precise and sensitive analytical technique for T4 concentration determination in in vitro studies.     

电感耦合等离子体质谱法测定手机壳套中14种可迁移元素

建立电感耦合等离子体质谱法测定手机壳套中14种可迁移元素含量的方法。样品经人工模拟汗液溶液振荡处理,使14种特定元素迁移至模拟溶液中,然后进行微波消解,采用电感耦合等离子体质谱法对消解液进行测定。14种元素在各自的质量浓度范围内具有良好的线性关系,相关系数均大于0.999,方法检出限为0.004~0.400μg/L。样品加标回收率为88.2%~99.5%,测定结果的相对标准偏差为2.5%~9.3%(n=5)。该方法操作简便,灵敏度高,线性范围广,定量准确,适用于手机壳套中14种可迁移元素含量的测定。     

Capillary electrophoresis inductively coupled plasma mass spectrometry

Chemical speciation (extraction of elemental information and identification of molecular environment for an analyte in a complex sample) has been a long sought after goal for analytical chemists. Recently, because of successful developments in more sensitive element-specific detectors and gentle separation schemes, which preserve the true chemical information in a real sample, routine speciation experiments are becoming a common occurrence in the scientific literature. For many reasons, the combination of capillary electrophoresis (for separation of different chemical species) with inductively coupled plasma mass spectrometry (for element and isotope specific detection) has emerged as the method of choice for these analyses. In this article the basic principles of capillary electrophoresis inductively coupled plasma mass spectrometry are discussed. Design consideration for instrument interface, anticipated difficulties with speciation experiments and applications for specific matrices and analytes are also presented in this article.     

Application of inductively coupled plasma sector field mass spectrometry for low-level environmental americium-241 analysis

An improved and novel sample preparation method for ²⁴¹Am analysis by inductively coupled plasma sector field mass spectrometry has been developed. The procedure involves a selective CaF₂ pre-concentration followed by an extraction chromatographic separation using TRU™ resin. The achieved absolute detection limit of 0.86 fg (0.11 mBq) is comparable to that of alpha spectrometry (0.1 mBq) and suitable for low-level environmental measurements. Analysis of different kinds of environmental standard reference materials (IAEA-384 - Fangataufa lagoon sediment, IAEA-385 - Irish Sea sediment and IAEA-308 - Mixed seaweed from the Mediterranean Sea) and alpha spectrometry were used to validate the procedure. The chemical recovery of sample preparation ranged between 72 and 94%. The results obtained are in good agreement with reference values and those measured by alpha spectrometry. The proposed method offers a rapid and less labor-intensive possibility for environmental ²⁴¹Am analysis than the conventionally applied radioanalytical techniques.     

Radionuclide determination in environmental samples by inductively coupled plasma mass spectrometry

The determination of naturally occurring and anthropogenic radionuclides in the environment by inductively coupled plasma mass spectrometry has gained recognition over the last fifteen years, relative to radiometric techniques, as the result of improvement in instrumental performance, sample introduction equipment, and sample preparation. With the increase in instrumental sensitivity, it is now possible to measure ultratrace levels (fg range) of many radioisotopes, including those with half-lives between 1 and 1000 years, without requiring very complex sample pre-concentration schemes. However, the identification and quantification of radioisotopes in environmental matrices is still hampered by a variety of analytical issues such as spectral (both atomic and molecular ions) and non-spectral (matrix effect) interferences and instrumental limitations (e.g., abundance sensitivity).The scope of this review is to highlight recent analytical progress and issues associated with the determination of radionuclides by inductively coupled plasma mass spectrometry. The impact of interferences, instrumental limitations (e.g., degree of ionization, abundance sensitivity, detection limits) and low sample-to-plasma transfer efficiency on the measurement of radionuclides by inductively coupled plasma mass spectrometry will be described. Solutions that overcome these issues will be discussed, highlighting their pros and cons and assessing their impact on the measurement of environmental radioactivity. Among the solutions proposed, mass and chemical resolution through the use of sector-field instruments and chemical reactions/collisions in a pressurized cell, respectively, will be described. Other methods, such as unique sample introduction equipment (e.g., laser ablation, electrothermal vaporisation, high efficiency nebulization) and instrumental modifications/optimizations (e.g., instrumental vacuum, radiofrequency power, guard electrode) that improve sensitivity and performance will also be examined.     

Determination of trace phosphorus in high purity tantalum materials by inductively coupled plasma mass spectrometry subsequent to matrix separation with on-line anion exchange/coprecipitation

An on-line matrix separation/inductively coupled plasma mass spectrometry (ICP-MS) method is proposed for the determination of trace amounts of phosphorus in high purity tantalum metal, tantalum (V) oxide, and tantalum pentaethoxide. In the present method, the matrix tantalum in the sample solution was adsorbed on the anion exchange resin, and phosphorus (phosphate ion) was eluted with the carrier solution of HF and HNO3 mixture. Then, the effluent solution was subsequently mixed with bismuth solution and aqueous ammonia solution to coprecipitate phosphate together with bismuth hydroxide. The precipitate formed was collected on the in-line membrane filter to wash out nitric acid with pure water, and then dissolved with hydrochloric acid. The obtained phosphorus sample solution was introduced directly into the nebulizer of ICP-MS for the determination of phosphorus. Phosphorus was determined at the molecular ion signal of 31P16O+ (m/z 47). The detection limit (3sigma) of phosphorus in the present method was 1.3 ng mL(-1) as the sample solution basis, and the relative standard deviation for 30 ng mL(-1) of phosphorus in the standard solution was 4.3% in the replicate measurements (n=11). The present method was applied to the analysis of high purity tantalum materials. The concentrations of phosphorus in tantalum samples were in fairly good agreement with those obtained by glow discharge mass spectrometry (GDMS).     

Micro-quantitative determination of ciprostene in plasma by gas chromatography-mass spectrometry coupled with an antibody extraction.

A simple and highly sensitive method has been developed for the determination in plasma of ciprostene, 9 beta-methyl-6 alpha-carbaprostaglandin I2, using gas chromatography-mass spectrometry following solid-phase extraction on an immobilized antibody column. The anti-ciprostene antibody obtained from rabbit serum was coupled to an agarose support matrix, and the immobilized antibody thus prepared was used as an extraction phase for sample clean-up. The extracted drug was treated with pentafluorobenzyl bromide followed by bis(trimethylsilyl)trifluoroacetamide. The derivative was quantitatively analysed by negative-ion chemical ionization gas chromatography-mass spectrometry. The lower limit of quantitation was 50 pg/ml when 1 ml of human plasma was used. The plasma concentration of ciprostene in a dog treated with ciprostene at 2.5 micrograms/kg was determined successfully by this method.     

Trace enrichment and measurement of platinum by flow injection inductively coupled plasma mass spectrometry

A flow injection system incorporating an alumina microcolumn has been coupled to inductively coupled plasma mass spectrometry (ICP-MS) for on-line preconcentration and determination of platinum (IV) in natural waters. Depending on the nature of the sample, a nominal preconcentration factor of up to 600 can be achieved by eluting with 50microl of 2 mol/l NH(4)OH. The limit of detection after a 5 min preconcentration time was 4 ngl(-1), with a relative standard deviation of 4% (100 ngl(-1) working solution). The proposed method was assessed for the determination of platinum (IV) in natural waters, motor car exhaust and some common analytical reagents.     

自动石墨消解–电感耦合等离子体质谱法同时测定左氧氟沙星胶囊中7种金属元素

建立自动石墨消解-电感耦合等离子体质谱法(ICP-MS)同时测定左氧氟沙星胶囊中铅、铬、砷、镉、锡、铝、铁7种金属元素含量的方法。以HNO3-H2O2()体积比为1∶1为消解体系,采用自动石墨消解法消解左氧氟沙星胶囊样品,消解液除酸后,用5%硝酸溶液定容至50 mL,采用电感耦合等离子体质谱法对消解液进行测定,以内标法定量。铅、铬、砷、镉、锡、铝、铁的质量浓度在0.05~20.0μg/mL范围内与质谱响应值成良好的线性关系,相关系数均大于0.998,方法检出限为0.119~1.323μg/kg。样品加标回收率为91.2%~105.5%,测定结果的相对标准偏差为1.67%~3.46%(n=6)。该方法样品前处理简单,检出限低,测定结果准确,适用于左氧氟沙星胶囊等沙星类抗生素中多种金属元素残留的测定。     

Multielement analysis of whole blood by high resolution inductively coupled plasma mass spectrometry

An analytical method using double focusing sector field inductively coupled plasma mass spectrometry (ICP-SMS) for rapid simultaneous determination of 50 elements in digested human blood is described. Sample preparation consisted of microwave digestion with nitric acid followed by dilution with ultrapure water. The importance of controlling possible contamination sources at different sample preparation and analysis stages in order to achieve adequate method detection limits (MDL) is emphasised. Correction for matrix effects was made using scandium, indium and lutecium as internal standards. Accuracy of the data for elements suffering from spectral interferences was improved by applying either a high resolution capability of the ICP-SMS or mathematical corrections. Different approaches for accuracy assessment in blood analysis are evaluated. Additional information on trace elements concentration in selected blood reference materials is given. The between-batch precision was assessed from replicate analysis (including sample preparation) of reference materials and was better than 10% RSD for 21 elements and better than 30% RSD for 36 elements under consideration. A statistical summary for results obtained for 31 blood samples from non-exposed subjects is presented. The majority of elements tested was found in the samples at concentrations higher than MDL.     

Rapid analysis of captopril in human plasma and pharmaceutical preparations by headspace solid phase microextraction based on polypyrrole film coupled to ion mobility spectrometry

A rapid, simple, and sensitive headspace solid phase microextraction coupled to ion mobility spectrometry (HS-SPME-IMS) method is presented for analysis of the highly specific angiotensin-converting enzyme (ACE) inhibitor, captopril (CAP). Positive ion mobility spectra of CAP were acquired with an ion mobility spectrometer equipped with a corona discharge ionization source. Mass-to-mobility correlation equation was used to identify product ions. A dodecylsulfate-doped polypyrrole (PPy-DS) coating was used as a fiber for SPME. The results showed that PPy-DS based SPME fiber was suitable for successfully extracting CAP from human blood plasma and pharmaceutical samples. The HS-SPME-IMS method provided good repeatability (R.S.D.s < 4%) for aqueous and spiked plasma samples. The calibration graphs were linear in the range of 10-300 ng mL⁻¹ (R² > 0.99) and detection limits were 7.5 ng mL⁻¹ for aqueous and 6.3 ng mL⁻¹ for plasma blank samples. Finally, a standard addition calibration method was applied to HS-SPME-IMS technique for the analysis of blood plasma samples and tablets. Purpose method seemed to be suitable for the analysis of CAP in plasma samples as it is not time consuming (state total time from sample preparation to analysis), it required only small quantities of the sample, and no derivatization was required.     

电感耦合等离子体质谱法(ICP-MS)测定废水中有害元素银的含量

为了寻求一种更加适合废水中低含量银的测定方法,本文采用石墨电热板消解-电感耦合等离子体质谱法测定废水中的低含量银离子。通过仪器工作条件最优化、测定线性回归方程、检出限、准确度、精密度、实际样品加标回收率,并与电感耦合等离子体发射光谱法（ICP-AES）的实际样品测定结果进行比对来评价该方法的实用性。石墨电热板消解-电感耦合等离子体质谱法前处理方法简便,分析速度快且该方法检出限较低,为0.03ug/L,标准样品测定的相对误差为-0.7%～1.7%,相对标准偏差为1.1%～2.5%,实际样品加标回收率在97.0%～103%之间,回收率高,能够满足废水中低含量银的测定。     

Preconcentration and determination of trace metals in seawater using a thiol cotton fiber minicolumn coupled with inductively coupled plasma mass spectrometry.

A rapid separation and preconcentration method was developed for the determination of trace metals Cu, Zn, Cd, and Pb in seawater using a minicolumn packed with thiol cotton fiber (TCF) coupled with inductively coupled plasma mass spectrometry (ICP-MS). Preconcentration parameters, such as seawater sample volume and flow rate and eluent hydrochloric acid concentration, volume and flow rate, were optimized. Under the optimized conditions, trace metals Cu, Zn, Cd, and Pb in seawater can be determined with no interference from saline matrices. When a sample volume of 1500 ml and a sample flow rate of 15 ml min(-1) were used, the preconcentration factor of 1500 and RSD value of <7% at ng ml(-1) were achieved. The accuracy of the recommended method was verified by the analysis of certified reference materials.     

Applications of inductively coupled plasma mass spectrometry and laser ablation inductively coupled plasma mass spectrometry in materials science

Inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) have been applied as the most important inorganic mass spectrometric techniques having multielemental capability for the characterization of solid samples in materials science. ICP-MS is used for the sensitive determination of trace and ultratrace elements in digested solutions of solid samples or of process chemicals (ultrapure water, acids and organic solutions) for the semiconductor industry with detection limits down to sub-picogram per liter levels. Whereas ICP-MS on solid samples (e.g. high-purity ceramics) sometimes requires time-consuming sample preparation for its application in materials science, and the risk of contamination is a serious drawback, a fast, direct determination of trace elements in solid materials without any sample preparation by LA-ICP-MS is possible. The detection limits for the direct analysis of solid samples by LA-ICP-MS have been determined for many elements down to the nanogram per gram range. A deterioration of detection limits was observed for elements where interferences with polyatomic ions occur. The inherent interference problem can often be solved by applying a double-focusing sector field mass spectrometer at higher mass resolution or by collision-induced reactions of polyatomic ions with a collision gas using an ICP-MS fitted with collision cell. The main problem of LA-ICP-MS is quantification if no suitable standard reference materials with a similar matrix composition are available. The calibration problem in LA-ICP-MS can be solved using on-line solution-based calibration, and different procedures, such as external calibration and standard addition, have been discussed with respect to their application in materials science. The application of isotope dilution in solution-based calibration for trace metal determination in small amounts of noble metals has been developed as a new calibration strategy. This review discusses new analytical developments and possible applications of ICP-MS and LA-ICP-MS for the quantitative determination of trace elements and in surface analysis for materials science.     

Multielement analysis of whole blood by high resolution inductively coupled plasma mass spectrometry

An analytical method using double focusing sector field inductively coupled plasma mass spectrometry (ICP-SMS) for rapid simultaneous determination of 50 elements in digested human blood is described. Sample preparation consisted of microwave digestion with nitric acid followed by dilution with ultrapure water. The importance of controlling possible contamination sources at different sample preparation and analysis stages in order to achieve adequate method detection limits (MDL) is emphasised. Correction for matrix effects was made using scandium, indium and lutecium as internal standards. Accuracy of the data for elements suffering from spectral interferences was improved by applying either a high resolution capability of the ICP-SMS or mathematical corrections. Different approaches for accuracy assessment in blood analysis are evaluated. Additional information on trace elements concentration in selected blood reference materials is given. The between-batch precision was assessed from replicate analysis (including sample preparation) of reference materials and was better than 10% RSD for 21 elements and better than 30% RSD for 36 elements under consideration. A statistical summary for results obtained for 31 blood samples from non-exposed subjects is presented. The majority of elements tested was found in the samples at concentrations higher than MDL. Received: 23 November 1998 / Revised: 6 January 1999 / Accepted: 12 January 1999