Impact of pump flow fluctuations on post column online ID-ICP-MS

In post column online isotope dilution mass spectrometry (IDMS), the stability of the spike mass flow is a key element. Changes in viscosity or fluctuations in the pump rate of the peristaltic pump may affect the results of post column online IDMS measurements. It was shown by simulating random fluctuations and studying the changes in the resulting integrals of the isotope ratio chromatogram of the sample that even small fluctuations, observable when using peristaltic pumps, can influence the result and especially its uncertainty. The use of a balance to continuously monitor the mass flow of the spike during the measurement which we presented in a previous publication allows now to correct the isotope ratio chromatogram for these fluctuations. Subsequently, the simulated effect was verified experimentally for the determination of Se-Met in the human serum reference material BCR 637, where the corrected mass fraction was plainly closer to the mass fraction obtained by species specific IDMS. Additional attention was paid to the fact that there is a time shift between the observation of the fluctuations in the pump rate and the detection of these fluctuations in the ICP-MS.     

同位素稀释法电感耦合等离子体质谱在痕量元素分析中的应用

介绍了同位素稀释法的原理,对同位素稀释法的浓度计算公式进行了推导。着重论述了同位素稀释法电感耦合等离子体质谱分析过程中影响同位素比值测定结果准确度和精确度的主要因素及其解决办法。综述了同位素稀释法电感耦合等离子体质谱近几年来在材料、生物以及环境样品分析中的应用。     

The determination of lead in blood using isotope dilution inductively coupled plasma mass spectrometry

Isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS) was applied to the certification of Pb in four levels of NIST blood SRM, 955a. This standard reference material (SRM) represents a significant improvement over the previous blood reference material and will greatly aid method development. The lowest level, 47.76 ng/g Pb was determined with analysis uncertainty (95% CI, ID-ICP-MS uncertainties) of less than 1% and the highest level, 517.9 ng/g Pb to 0.3%. Uncertainty in the lowest level was due to sample inhomogeneity and variability in the analytical blank as the RSD on ratio measurements was typically better than 0.2%. Properly applied isotope dilution coupled with careful isotope ratio measurements on the ICP-MS offers precision and accuracy for blood Pb analyses beyond what is currently obtainable with routine methods.     

高效液相色谱-非特异性同位素稀释质谱联用技术定量分析全血中总血红蛋白含量

建立了基于同位素稀释(ID)的高效液相色谱(HPLC)-电感耦合等离子体质谱(ICP-MS)联用技术, 通过测量血红蛋白(HGB)中铁(Fe)元素含量实现了全血中总HGB准确定量的策略. 该策略包括2种方法, 第一种方法为在线HPLC-ID-ICP-MS定量技术: 全血中HGB经液相色谱分离后, 通过柱后在线添加浓缩⁵⁴Fe同位素稀释剂的方式, 与液相色谱洗脱液经三通混合后进入ICP-MS在线测量⁵⁴Fe/⁵⁶Fe的同位素比值, 并根据同位素稀释质谱法公式及蛋白中Fe的含量计算HGB的浓度. 针对全血样品中存在的其它主要含铁蛋白[如转铁蛋白(Tf)], 在实现色谱完全分离的基础上, 通过在线优化改变⁵⁴Fe稀释剂流速实现了HGB和Tf的同时定量. 在另一种方法中, 先对全血样品进行消解并通过ID-ICP-MS测定其中Fe的总量, 然后根据全血样品的HPLC-ICP-MS分析结果, 通过计算HGB质谱峰面积占总峰面积的比值从而得到HGB中Fe含量占总Fe含量的比例, 实现了其中HGB的准确定量. 2种定量方法得到的结果分别为(115.3±2.4) mg/g和(115.5±2.1) mg/g, 结果吻合良好, 方法的检出限为1.0×10^?7 mg/g, 方法精密度RSD均<3%. 2种方法均经过HGB标准物质IRMM/IFCC-467进行验证, 测量结果在标准值不确定度范围之内, 可作为临床检验领域HGB分析的参考测量方法.     

Chromatographic methods for the quantification of free and chelated gadolinium species in MRI contrast agent formulations

Speciation measurements of gadolinium in liposomal MRI contrast agents (CAs) are complicated by the presence of emulsifiers, surfactants, and therapeutic agents in the formulations. The present paper describes two robust, hyphenated chromatography methods for the separation and quantification of gadolinium in nanoemulsion-based CA formulations. Three potential species of gadolinium, free gadolinium ion, gadolinium chelated by diethylenetriamine pentaacetic acid, and gadolinium chelated by 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-diethylenetriaminepentaacetic acid, were present in the CA formulations. The species were separated by reversed-phase chromatography (reversed phase high-performance liquid chromatography, RP-HPLC) or by high-pressure size-exclusion chromatography (HPSEC). For RP-HPLC, fluorescence detection and post-column online isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS) were used to measure the amount of gadolinium in each species. Online ID-ICP-MS and species-specific isotope dilution (SID)-ICP-MS were used in combination with the HPSEC column. The results indicated that some inter-species conversions and degradation had occurred within the samples and that SID-ICP-MS should be used to provide the most reliable measurements of total and speciated gadolinium. However, fluorescence and online ID-ICP-MS might usefully be applied as qualitative, rapid screening procedures for the presence of free gadolinium ions.     

Determination of (187)Os in molybdenite by ICP-MS with neutron-induced (186)Os and (188)Os spikes

The article describes a method for the determination of (187)Os in molybdenite by isotope dilution inductively coupled plasma-mass spectrometry (ID-ICP-MS) with neutron-induced (186)Os and (188)Os spike. The spike used in the present work was prepared in line with the principle by which artificial nuclides are produced in a nuclear reaction. The concentration and isotopic composition of osmium in the prepared spike were evaluated accurately with the isotope dilution method, using negative thermal ion mass spectrometry (N-TIMS). The advantage of this method is that using (186)Os and (188)Os double spikes can effectively compensate for the mass discrimination effects of ICP-MS. Thus, the common correction practice for mass bias in the isotope dilution method with a single spike is unnecessary. In addition, the method enables one to reduce the determined error arising from instrumental instability. The precision for the (187)Os/((186)Os+(188)Os) ratio was approximately 2% (2sigma, RSD), but in the case of (187)Os/(186)Os, (187)Os/(188)Os and (186)Os/(188)Os, precision ranged from 2.0 to 8% (2sigma, RSD). The results for (187)Os concentration in a molybdenite sample determined with this method showed good agreement with reference values.     

同位素稀释等离子体质谱法测定地质样品中痕量硼

建立了同位素稀释等离子体质谱法（ID—ICP—MS）测定地质样品中痕量硼的方法。采用减压排空色谱柱分离样品中的大量基体,以减少基体效应的影响,具有试剂用量少、分离速度快、效果好等特点。对两个标准物质GSD-4和GSD-8的测定结果表明,其与参考值吻合得较好,相对偏差均小于6％。3个不同样品的测定结果表明,该方法具有较好的准确度和精密度。     

同位素稀释电感耦合等离子体质谱法分析降尘中铂族元素

选取(195)Pt和(108)Pd为待测同位素,(196)pt和(105)Pd为富集同位素,同位素稀释电感耦合等离子质谱法(ID-ICP-MS)测定降尘样品中(195)Pt/(196)Pt和(108)Pd/(105)Pd比值,分析样品中Pt和Pd含量.利用Dowex AG50W-8阳离子交换和N-苯甲酰-N苯基羟胺(B...     

Evaluation of online carbon isotope dilution mass spectrometry for the purity assessment of synthetic peptide standards

We present a novel method for the purity assessment of peptide standards which is applicable to any water soluble peptide. The method is based on the online ¹³C isotope dilution approach in which the peptide is separated from its related impurities by liquid chromatography (LC) and the eluent is mixed post-column with a continuous flow of ¹³C-enriched sodium bicarbonate. An online oxidation step using sodium persulfate in acidic media at 99 °C provides quantitative oxidation to ¹²CO₂ and ¹³CO₂ respectively which is extracted to a gaseous phase with the help of a gas permeable membrane. The measurement of the isotope ratio 44/45 in the mass spectrometer allows the construction of the mass flow chromatogram. As the only species that is finally measured in the mass spectrometer is CO₂, the peptide content in the standard can be quantified, on the base of its carbon content, using a generic primary standard such as potassium hydrogen phthalate. The approach was validated by the analysis of a reference material (NIST 8327), and applied to the quantification of two commercial synthetic peptide standards. In that case, the results obtained were compared with those obtained using alternative methods, such as amino acid analysis and ICP-MS. The results obtained proved the value of the method for the fast, accurate and precise mass purity assignment of synthetic peptide standards.     

同位素稀释电感耦合等离子体质谱(ID-ICP-MS)测定植物与人发标准物质中的铅

建立了同位素稀释电感耦合等离子体质谱(ID-ICP-MS)测定铅的方法.考察和讨论了仪器参数对同位素比值测定的影响,优化了仪器的数据采样参数.利用内标Tl对质量歧视、系统漂移进行了校正.讨论了同位素浓缩剂加入量对最终浓度测定值的不确定度的影响.将该方法应用于植物标准物质和人发标准物质的测定,结果令人满意.     

Determination of Mercury in Urine and Seawater by Flow Injection Vapor Generation Isotope Dilution Inductively Coupled Plasma Mass Spectrometry

A simple and inexpensive laboratory-built vapor generator was used with inductively coupled plasma mass spectrometry (ICP-MS) for the determination of mercury in urine and seawater samples. The applications of vapor generation ICP-MS alleviated the non-spectroscopic interferences and the sensitivity problem of mercury determination encountered when the conventional pneumatic nebulizer was used for sample introduction. The concentration of mercury was determined by isotope dilution method. The isotope ratio of mercury was calculated from the peak areas of each injection peak. The repeatability of the peak areas and isotope ratio determinations of seven consecutive injections of 1 ng mL^?1 Hg solution were 2.3% and 2.2%, respectively. This method has a detection limit of 0.07 ng mL^?1 for mercury. This method was applied to determine mercury in a CASS-3 nearshore seawater reference sample, NASS-4 open ocean seawater reference sample, NIST SRM 2670 freeze-dried urine reference sample and several urine and seawater samples collected from National Sun Yat-Sen University. The results for the reference samples agreed satisfactorily with the reference values. Results for other samples analyzed by the isotope dilution method and the method of standard additions agreed satisfactorily. Precision was better than 10% for most of the determinations.     

Isotope ratio mass spectrometry coupled to liquid and gas chromatography for wine ethanol characterization

Two new procedures for wine ethanol 13C/12C isotope ratio determination, using high-performance liquid chromatography and gas chromatography isotope ratio mass spectrometry (HPLC/IRMS and GC/IRMS), have been developed to improve isotopic methods dedicated to the study of wine authenticity. Parameters influencing separation of ethanol from wine matrix such as column, temperature, mobile phase, flow rates and injection mode were investigated. Twenty-three wine samples from various origins were analyzed for validation of the procedures. The analytical precision was better than 0.15 per thousand, and no significant isotopic fractionation was observed employing both separative techniques coupled to IRMS. No significant differences and a very strong correlation (r = 0.99) were observed between the 13C/12C ratios obtained by the official method (elemental analyzer/isotope ratio mass spectrometry) and the proposed new methodology. The potential advantages of the developed methods over the traditional one are speed (reducing time required from hours to minutes) and simplicity. In addition, these are the first isotopic methods that allow 13C/12C determination directly from a liquid sample with no previous ethanol isolation, overcoming technical difficulties associated with sample treatment.     

Fast gel permeation chromatography–mass spectrometry method for polymer and additive analysis

This study presents gel permeation chromatography (GPC) coupled with mass spectrometry (MS) as a suitable method to evaluate molecular weight distribution, oligomeric structure, and additives of commercial polystyrene resins in just 4?min. The chromatogram recorded by ultraviolet (UV) detection gives information on the high molecular mass fractions, while the mass detector provides knowledge on the chemical structure and concentration of oligomers and additives. A good agreement for the average molecular weights of the broad polystyrene reference SRM 706 and an excellent correlation with the expected isotope distributions for oligomers and additives were obtained using this fast GPC–UV–MS method.     

A new gas inlet system for an isotope ratio mass spectrometer improves reproducibility

We have developed a new inlet system for a gas sample isotope ratio mass spectrometer (IRMS). It is based on the well-known open split design from the gas chromatography/mass spectrometry (GC/MS) system due to its simplicity. The advantages over the conventional double inlet system with the metal bellows design include an improved reproducibility mainly due to a highly controllable pressure and temperature adjustment, a markedly lowered memory effect due to an uninterrupted gas flow through the ion source which limits adsorption/desorption processes on surfaces, and a single inlet capillary circumventing problems of asymmetrical behavior of sample and reference inlet paths. Furthermore, sample consumption is of the same order as for conventional measurements (i.e. about 0.4 mmol per hour), of which however only 2 &mgr;mol/h is used for the actual isotope ratio determination since the major gas amount acts as a gas flow seal against the atmosphere, corresponding to a 100-200 fold overkill. This may be improved in future systems. Copyright 2000 John Wiley & Sons, Ltd.     

Quantitative method for analysis of tobacco‐specific N‐nitrosamines in mainstream cigarette smoke by using heart‐cutting two‐dimensional liquid chromatography with tandem mass spectrometry

A heart‐cutting two dimensional liquid chromatography coupled with tandem mass spectrometry method was developed for the analysis of tobacco‐specific N‐nitrosamines (TSNAs) at low concentration level in Virginia‐type cigarette smoke. A strong cation exchange column was utilized for the first dimensional separation, which effectively removed acidic and neutral components in the smoke, followed by a reversed phase liquid chromatography coupled with tandem mass spectrometric analysis. To capture components of the TSNAs in the effluent on the trapping column, a compensating pump was applied for online dilution and pH adjustment during the period of the TSNAs fraction transferring and enrichment. Highly sensitive determination of the TSNAs in mainstream cigarette smoke was achieved by isotope deuterated internal standards under the multiple reaction monitoring mode. Compared with traditional methodologies, the method was almost no matrix interference. Limits of quantity for the TSNAs were within 0.027–0.094 ng/mL, and the results showed good reproducibility and accuracy. Finally, the new method was applied for analysis of the Kentucky reference cigarettes and the results agreed well with joint experiments of Cooperation Centre for Scientific Research Relative to Tobacco.     

Characterization of sealed radioactive sources: uncertainty analysis to improve detection methods

A radioactive ¹³⁷Cs source has been analyzed for the radioactive parent ¹³⁷Cs and stable decay daughter ¹³⁷Ba. The ratio of the daughter to parent atoms is used to estimate the date when Cs was purified prior to source encapsulation (an “age” since purification). The isotopes were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) after chemical separation. In addition, Ba was analyzed by isotope dilution ICP-MS (ID-ICP-MS). A detailed error analysis of the mass spectrometric work has been undertaken to identify areas of improvement, as well as quantifying the effect the errors have on the “age” determined. This paper reports an uncertainty analysis to identifying areas of improvement and alternative techniques that may reduce the uncertainties. In particular, work on isotope dilution using ICP-MS for the “age” determination of sealed sources is presented. The results will be compared to the original work done using external standards to calibrate the ICP-MS instrument.     

Development of an on-line isotope dilution technique with HPLC/ICP-MS for the accurate determination of elemental species

An on-line isotope dilution technique has been developed for use with a high performance liquid chromatography system (HPLC) coupled to an inductively coupled plasma mass spectrometer (ICP-MS). With this method it is possible to characterize elemental species at low concentration levels and to quantify them accurately. The possibilities of this method are shown using the examples of the determination of the interactions of different molecular weight fractions of dissolved organic matter (DOM) with copper and molybdenum in a natural water sample.     

Simplified method for the Re-Os dating of molybdenite using acid digestion and isotope dilution ICP-MS

An analytical method was developed for Os-Re dating of molybdenite. The method is based on determination of Os and Re concentrations in molybdenite by isotope dilution inductively-coupled plasma mass spectrometry (ID-ICP-MS). Sample digestion and sample/spike equilibration were achieved by a two-stage autoclave-based procedure using a mixture of nitric and sulphuric acids. Os was separated from the sample digest by modified single-stage distillation of osmium tetraoxide (OsO₄) using elevated temperature and on-line addition of hydrogen peroxide. OsO₄(g) was trapped in a mixture of 0.05% thiourea in 0.05 M sodium hydroxide. An anion-exchange column was used to separate Re from excess Mo in the solution remaining after distillation. Os and Re isotope ratio measurements were performed by single-collector, double focusing inductively-coupled plasma mass spectrometry (ICP-MS) with on-line mass-bias correction. Typical instrumental precision was in the range 0.02-0.2% relative standard deviation (R.S.D.) depending on the analyte concentrations. Notorious Os memory effects in the ICP-MS introduction system were eliminated using 5% ammonia solution, both as matrix for final dilution of the trap mixture as well as for washing between the samples. The reproducibility of the entire analytical procedure was accessed by replicate dating of two molybdenite standards and three molybdenite separates, and was found to be in the range 0.87-1.52% R.S.D. Though accuracy of the method is limited by difficulties in evaluating exact concentration of Os in spike solution, ages obtained in the course of these work agrees well with previously published data.     

Precise and traceable carbon isotope ratio measurements by multicollector ICP-MS: what next?

This article reviews recent developments in the use of multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS) to provide high-precision carbon isotope ratio measurements. MC-ICP-MS could become an alternative method to isotope ratio mass spectrometry (IRMS) for rapid carbon isotope ratio determinations in organic compounds and characterisation and certification of isotopic reference materials. In this overview, the advantages, drawbacks and potential of the method for future applications are critically discussed. Furthermore, suggestions for future improvements in terms of precision and sensitivity are made. No doubt, this is an exciting analytical challenge and, as such, hurdles will need to be cleared.     

Determination of As, Cd, Cr, and Hg in SRM 2584 (trace elements in indoor dust) by high-resolution inductively coupled plasma mass spectrometry

Standard reference material (SRM) 2584 (Trace Elements in Indoor Dust) was developed as a reference standard for evaluating field methods and for validating laboratory and reference methods for the assessment of lead contamination and exposure. In addition to lead, the toxic trace elements As, Cd, Cr, and Hg, at approximately 17, 10, 140, and 5 microg g(-1), respectively, have been certified in the SRM. These four analytes were successfully determined by use of high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). Isobaric interferences at masses of As and Cr were resolved by using the high resolution mode (nominal 8000) and the medium resolution mode (nominal 3000), respectively, of the instrument. The effects of a significant drift in analyte sensitivity in the course of measurement were rectified by use of internal standardization, single spike standard addition, and an optimized analysis sequence. The results were compared with those obtained by instrumental neutron activation analysis (INAA) and isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). The results for the quality control, SRM 2704 (Buffalo River Sediment), were in good agreement with the certified values, indicated by the uncertainty intervals of the measured values overlapping the certified intervals at 95% confidence level.