Achieving traceable chemical measurements: inter-laboratory evaluation of a simplified technique for isotope dilution mass spectrometry. Part 2. Methodology for high accuracy analysis of organic analytes

A high accuracy measurement procedure developed and validated at LGC has been transferred to a number of expert UK laboratories, and their experience in applying the technique has been evaluated by inter-laboratory comparisons. It is an “exact matching” calibration procedure for analysis of organic analytes using isotope dilution mass spectrometry (IDMS). This calibration procedure uses a calibration blend and a sample blend with closely matched isotope amount ratios, and is an iterative process, culminating in the calibration blend and sample blend having identical isotope amount ratios. It is capable of high accuracy, since systematic errors in the determination of the isotope amount ratios are cancelled out. A series of four inter-laboratory comparisons of increasing difficulty were carried out involving a number of expert laboratories. The first three comparisons used gas chromatography mass spectrometry (GC–MS) analysis of the pesticide metabolite (pp′-dichlorodiphenyl) dichloroethylene (pp′-DDE), involving both conventional calibration and IDMS exact matching procedures for pp′-DDE in a solvent and a complex liquid matrix (corn oil). The fourth comparisons utilised liquid chromatography mass spectrometry (LC–MS) and involved the analysis of sulphamethazine (4-amino-N-(4,6 dimethyl-2 pyrimidinyl) benzenesulphonamide) in solvent using IDMS and conventional calibration techniques. Following the first trial, a workshop for participants was held on the use of the exact matching procedure together with a short course on uncertainty estimation. The results of the comparisons clearly showed the superior accuracy of using IDMS with the exact matching procedure for both GC–MS and LC–MS applications. These comparisons and the workshop have enabled the methodology to be transferred to UK industry, helping to improve UK measurement capability.     

Achieving traceable chemical measurements: inter-laboratory evaluation of a simplified technique for isotope dilution mass spectrometry (IDMS). Part 1: Methodology for high accuracy analysis of trace metals

A high accuracy measurement procedure developed and validated at the Laboratory of the Government Chemist (LGC) has been transferred to a number of expert United Kingdom laboratories and their experience in applying the technique has been evaluated by inter-laboratory comparisons. It is an approximate matching calibration procedure for analysis of trace metals using isotope dilution mass spectrometry (IDMS). Use of a calibration blend and a sample blend having closely matched isotope amount ratios reduces systematic errors. Four comparisons were carried out, each evaluating an increasingly difficult aspect of the methodology. The final study required determination of trace levels of cadmium in an artificial food matrix acid digest containing tin, using both external calibration and approximate matching IDMS. The results of the trials clearly showed the superior accuracy of the IDMS approximate matching procedure; a result within 1% of the target reference value could be achieved. These trials and a training workshop enabled LGC to transfer its methodology to other expert laboratories, helping to improve the United Kingdom delivery of traceable reference measurements.     

Comparison of standard addition and conventional isotope dilution mass spectrometry for the quantification of endogenous progesterone in milk

In this study, a standard addition–isotope dilution mass spectrometry (SA-IDMS) method for quantification of endogenous progesterone in milk has been described. The method validation results, linearity, limits of detection and quantification, recovery and uncertainty were fit for the purpose of assigning reference mass fractions to proficiency testing schemes. The developed technique was compared to the isotope dilution mass spectrometry (IDMS) method already existing in the laboratory. Analytical results of two milk samples were (1.377 ± 0.048) μg/kg and (4.457 ± 0.155) μg/kg by SA-ID-LC/MS method, while the results were (1.355 ± 0.019) μg/kg and (4.359 ± 0.059) μg/kg by ID-LC/MS, respectively. Since SA-IDMS was an effective quantitative method that overcame matrix effect, similar quantitative results from IDMS and SA-IDMS indicated that the quantification of progesterone in milk was barely influenced by matrix. Both IDMS and SA-IDMS could be used to assign reference mass fractions to progesterone in milk inter-laboratory proficiency testing schemes.     

Isotope pattern deconvolution-tandem mass spectrometry for the determination and confirmation of diclofenac in wastewaters

Isotope dilution mass spectrometry (IDMS) based on isotope pattern deconvolution (IPD) has been applied here to MS/MS (QqQ) in order to carry out the quantification and confirmation of organic compounds in complex matrix water samples without the use of a methodological IDMS calibration graph. In this alternative approach, the isotope composition of the spiked sample is measured after fragmentation by SRM and deconvoluted into its constituting components (molar fractions of natural abundance and labeled compound) by multiple linear regression (IPD). The procedure has been evaluated for the determination of the pharmaceutical diclofenac in effluent and influent urban wastewaters and fortified surface waters by UHPLC (ESI) MS/MS using diclofenac-d₄ as labeled compound. Calculations were performed acquiring a part and the whole fragment cluster ion, achieving in all cases recoveries within 90–110% and coefficients of variation below 5% for all water samples tested. In addition, potential false negatives arising from the presence of diclofenac-d₂ impurities in the labeled compound were avoided when the proposed approach was used instead of the most usual IDMS calibration procedure. The number of SRM transitions measured was minimized to three to make possible the application of this alternative technique in routine multi-residue analysis.     

New mathematical models with associated equations for isotope dilution mass spectrometry (IDMS)

Vector models which progressively lead to a general model for isotope dilution mass spectrometry (IDMS) are presented for the case of two 'monitor isotopes' and one blend involved. They enable one to find the boundary conditions for performing IDMS, and cover the cases of highly enriched isotopes, radioactive isotopes and ratios that are given with different denominator. The models identify the key measurements in their simplest form as well as the conditions which minimise the measurement effort and in some cases the propagated measurement uncertainties. The equations are discussed and compared with other published IDMS equations. Combined with discussion on fundamental aspects of IDMS, this results in an even more 'general' but also more complex IDMS equation.     

Application of isotope dilution mass spectrometry to research of certified reference materials

This paper briefly describes the method and applications of isotope dilution mass spectrometry(IDMS). Primary standard solutions with various natural isotope abundances were used to certify the concentration of enriched isotope solutions by IDMS. Then these enriched isotopes were used to certify unknown samples by IDMS. Li, K, Mg, Fe, Cu, Ni, Cd, Mo, Pb, etc in CRMs were certified and very good results were obtained in three international comparisons by IDMS. Received: 15 June 2000 Accepted: 26 October 2001     

微量气体大小球三步同位素稀释质谱法理论探讨与实验模型设计

提出了一种适用于微量气体定量分析的大小球三步同位素稀释质谱法,并给出其实验模型和不确定度理论分析结果。通过引入三步稀释过程,不涉及稀释剂的纯度、丰度、添加质量等方面的数据,仅需测定各步稀释剂质量之比,在其中的两步反稀释过程中使用了基标准纯物质,从而使微量气体的定量分析结果可溯源至基标准纯物质。该方法解决了已有同位素稀释质谱法在微量气体定量分析中的难题。     

Improved sample preparation of glyphosate and methylphosphonic acid by EPA method 6800A and time‐of‐flight mass spectrometry using novel solid‐phase extraction

The employment of chemical weapons by rogue states and/or terrorist organizations is an ongoing concern in the United States. The quantitative analysis of nerve agents must be rapid and reliable for use in the private and public sectors. Current methods describe a tedious and time‐consuming derivatization for gas chromatography–mass spectrometry and liquid chromatography in tandem with mass spectrometry. Two solid‐phase extraction (SPE) techniques for the analysis of glyphosate and methylphosphonic acid are described with the utilization of isotopically enriched analytes for quantitation via atmospheric pressure chemical ionization–quadrupole time‐of‐flight mass spectrometry (APCI‐Q‐TOF‐MS) that does not require derivatization. Solid‐phase extraction‐isotope dilution mass spectrometry (SPE‐IDMS) involves pre‐equilibration of a naturally occurring sample with an isotopically enriched standard. The second extraction method, i‐Spike, involves loading an isotopically enriched standard onto the SPE column before the naturally occurring sample. The sample and the spike are then co‐eluted from the column enabling precise and accurate quantitation via IDMS. The SPE methods in conjunction with IDMS eliminate concerns of incomplete elution, matrix and sorbent effects, and MS drift. For accurate quantitation with IDMS, the isotopic contribution of all atoms in the target molecule must be statistically taken into account. This paper describes two newly developed sample preparation techniques for the analysis of nerve agent surrogates in drinking water as well as statistical probability analysis for proper molecular IDMS. The methods described in this paper demonstrate accurate molecular IDMS using APCI‐Q‐TOF‐MS with limits of quantitation as low as 0.400 mg/kg for glyphosate and 0.031 mg/kg for methylphosphonic acid. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of Urea in Milk by Liquid Chromatography-Isotope Dilution Mass Spectrometry

A definitive method based on liquid chromatography isotope dilution mass spectrometry (LC-IDMS) has been developed for the determination of milk urea, an indicator of nutrition status for the lactating animals. The milk samples were treated twice by sequentially adding acetonitrile and chloroform to precipitate proteins and then were directly separated using normal phase liquid chromatography without chemical derivatization. After the matrix separation, exact matching IDMS was used for the determination of milk urea, with high accuracy, high precision, good linearity and low uncertainty. The recoveries obtained for the four spiked milk samples were 100.6–102.2%. The linear range of signal responses was 10–2000 mg · kg^?1 with a linearity coefficient of 0.9995. The intraday and interday precisions in terms with relative standard deviations (RSDs) were 0.17–0.38% and 0.28–0.40%, respectively. The uncertainties of the whole sample analysis process were estimated to be 0.83%, 0.60%, and 0.64% for three samples with concentrations of 151.28, 184.36, and 266.66 mg · kg^?1.     

Development of a routine method for the simultaneous confirmation and determination of clenbuterol in urine by minimal labeling isotope pattern deconvolution and GC-EI-MS

A novel and fast routine method for the simultaneous determination and confirmation of clenbuterol in bovine and human urine samples by gas chromatography electron ionization mass spectrometry (GC-EI-MS) has been developed. The method employs isotope dilution mass spectrometry (IDMS) and is based on a combination of minimal labeling (a single ¹³C label in the molecule) and isotope pattern deconvolution (IPD). This new methodology does not require the construction of a methodological calibration graph, and was compared with the classical IDMS procedure employed in clenbuterol analysis based on the use of a deuterated compound as internal standard (d₉-clenbuterol) and a calibration curve. The sample preparation consists of simple extraction with dichloromethane, which was dried and derivatized with chloro(chloromethyl)dimethylsilane, generating a cyclic dimethylsilamorpholine (DMS) derivative suitable for GC(EI)MS detection and identification. This compound produces five intense ions in the electron ionization source, which allow the presence of clenbuterol to be confirmed in just one analysis, as demanded by European Union directives. The accuracy of the method was studied by performing recovery experiments at different concentration levels (from 0.3 to 5 ng g⁻¹) in 5 mL bovine urine samples using two labeled compounds: an in-house-synthesized ¹³C₁-clenbuterol and a commercially available d₉-clenbuterol. The detection limit of the method in human urine was 0.050 ng g⁻¹ with a sample volume of 10 mL, and is thus suitable for antidoping control purposes. Finally, the ¹³C₁-clenbuterol standard was employed for the determination of clenbuterol in two reference materials, BCR-503 and BCR-504 (lyophilized bovine urine). The concentrations obtained were in agreement with the certified values, with a reproducibility of below 1% RSD.     

Isotope-dilution ICP–MS for trace element determination and speciation: from a reference method to a routine method?

This critical review discusses the conditions under which inductively coupled plasma–isotope dilution mass spectrometry (ICP–IDMS) is suitable as a routine method for trace element and element-speciation analysis. It can, in general, be concluded that ICP–IDMS has high potential for routine analysis of trace elements if the accuracy of results is of predominant analytical importance. Hyphenated techniques with ICP–IDMS suffer both from lack of commercially available isotope-labeled spike compounds for species-specific isotope dilution and from the more complicated system set-up required for species-unspecific ICP–IDMS analysis. Coupling of gas or liquid chromatography with species-specific ICP–IDMS, however, enables validation of analytical methods involving species transformations which cannot easily be performed by other methods. The potential and limitations of ICP–IDMS are demonstrated by recently published results and by some unpublished investigations by our group. It has been shown that possible loss of silicon as volatile SiF₄ during decomposition of a sample by use of hydrofluoric acid has no effect on trace silicon determination if the isotope-dilution step occurs during digestion in a closed system. For powder samples, laser ablation ICP–IDMS can be applied with an accuracy comparable with that only available from matrix-matched standardization, whereas the accuracy of electrothermal vaporization ICP–IDMS was strongly dependent on the element determined. The significance of easy synthesis of isotope-labeled spike compounds for species-specific ICP–IDMS is demonstrated for monomethylmercury and Cr(VI). Isotope-exchange reactions between different element species can prevent the successful application of ICP–IDMS, as is shown for iodinated hydrocarbons. It is also shown for monomethylmercury that species transformations during sample-pretreatment steps can be followed by species-specific ICP–IDMS without loss of accuracy. A relatively simple and time-efficient procedure for determination of monomethylmercury in environmental and biological samples is discussed. The method, which entails a rapid microwave-assisted isotope dilution step and in-situ extraction of the derivatized species, has good potential for routine application in the future.     

The analysis of thyroxine in human serum by an 'exact matching' isotope dilution method with liquid chromatography/tandem mass spectrometry

A method for the analysis of thyroxine in human serum, utilising 'exact matching' isotope dilution mass spectrometry (IDMS) in combination with liquid chromatography/tandem mass spectrometry (LC/MS/MS), has been developed with a limit of quantification of 0.5 ng g(-1) of thyroxine in human serum. The extraction and clean-up of thyroxine from serum involves an efficient protein-precipitation stage followed by a solid-phase extraction procedure to produce an extract essentially free from interfering compounds. The method is reproducible, with expanded uncertainties of less than 2%, and is relatively fast to perform.     

Low uncertainty reverse isotope dilution ICP-MS applied to certifying an isotopically enriched Cd candidate reference material: A case study

An analytical method is presented based on reverse isotope dilution single detector inductively coupled plasma magnetic sector mass spectrometry (ID-ICP-SMS) and applied to the specific case of the certification of a (111)Cd enriched candidate Cd spike calibration material (nominal mass fraction 10 mg kg(-1) in 5% HNO3 solution). Uncertainty propagation was used as a tool for both determining the analytical approach and validating it. The robustness of close to "exact matching" reverse IDMS to correction of measured isotope intensities for multiplicative (mass discrimination) and (semi)additive effects (dead time, instrumental background, and isobaric interference) is discussed. The very low experimental relative standard deviation of the mean (0.08%) of eight replicate determinations indicated that all significant sources of uncertainty had probably been taken into account for the estimation of the final combined uncertainty statement (U(c) = 0.17%, k = 1). IRMM-621 was used as comparator. Uncertainties on IUPAC isotopic abundances of 111Cd and 112Cd, for the natural Cd solution involved between the two enriched materials, formed nearly 60% of U(c). The repeatability of the isotope ratio measurements contributed less than 10%. Correction for procedural blank necessitated somewhat unusual calculations (potential contamination of an enriched material with natural Cd). The procedure also involved a quadrupole based ICP-MS judged to be appropriate for the characterization of the isotopic composition. For comparison purposes, direct IDMS results are simulated using identical experimental input data. Finally, a significant background signal in the 106-116 mass region, observed only with the magnetic sector instrument, was attributed to argon based isobaric interferences.     

Bias reduction in the quantitative analysis of a target analyte present in a limited quantity in human plasma using dual-mode heart-cutting two-dimensional liquid chromatography coupled with isotope dilution mass spectrometry

Dual-mode heart-cutting two-dimensional liquid chromatography (DMHC 2D-LC) was applied to isotope dilution mass spectrometry (IDMS) to reduce the bias in the quantitative analysis of a target analyte present in a limited quantity in human plasma. Based on a Waters I-Class LC system, the DMHC 2D-LC system was operated in one- and two-dimensional modes to facilitate the determination of heart-cutting time and the efficient trapping of the target LC eluate. Experiments to determine the feasibility of coupling with IDMS were performed with triple quadrupole mass spectrometry using folic acid standards and/or ¹³C₅-folic acid. To validate the performance of the DMHC 2D-LC/IDMS system on a complex sample, human plasma was analyzed for folic acid and the result was compared with that obtained using conventional single-column LC. The total run time of the DMHC 2D-LC system was 20 min, the same as that of the single-column LC system. The peak profile of the spiked ¹³C₅-folic acid obtained with single-column LC/MS was affected by matrix effects, but resolved with DMHC 2D-LC/MS, thus improving the accuracy of the analysis. The DMHC 2D-LC/IDMS system showed reliable performance in analyzing the target analyte in human plasma, eliminating matrix effects and saving analysis time.     

Determination of melamine in milk powder using gas chromatography-high-resolution isotope dilution mass spectrometry

A GC-high-resolution isotope dilution MS (IDMS) method for the quantification of melamine in milk powder is described. The developed technique is compared to the LC-IDMS/MS technique, typically used for the determination of melamine in various matrices. The accuracy of the GC-high-resolution IDMS method was demonstrated when a small degree of equivalence was obtained in a regional comparative study involving the determination of melamine in milk powder.     

Synthesis and characterization of isotopically enriched methylmercury (CH3201Hg+)

A simple procedure for the synthesis of an important standard, isotopically enriched methylmercury, which is not commercially available, has been established successfully. The isotopically enriched standard synthesized is utilized in conventional isotope dilution mass spectrometry (IDMS), as well as in speciated IDMS (SIDMS), for determination of the true concentration of methylmercury in environmental samples. The CH₃²⁰¹Hg⁺ standard has been synthesized from commercially available ²⁰¹HgO and tetramethyltin. The synthesis time required is 1 h at 60°C. The product is highly pure, yielding more than 90% as ²⁰¹Hg in CH₃²⁰¹Hg⁺. Hazardous dimethylmercury does not occur during this synthesis procedure. The product synthesized was analyzed using high‐performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (ICP‐MS) and ICP‐MS alone in order to determine its concentration, isotopic composition and purity. The stability of the product was also evaluated for over 6 months and found to be stable at 4°C in the dark. The isotopically enriched methylmercury synthesized can be used in SIDMS and IDMS analyses as a standard. Copyright © 2003 John Wiley & Sons, Ltd.     

Development of a candidate certified reference material of cypermethrin in green tea

This paper presents the preparation of a candidate certified reference material (CRM) of cypermethrin in green tea, GLHK-11-01a according to the requirements of ISO Guide 34 and 35. Certification of the material was performed using a newly developed isotope dilution mass spectrometry (IDMS) approach, with gas chromatography high resolution mass spectrometry (GC–HRMS) and gas chromatography–tandem mass spectrometry (GC–MS/MS). Statistical analysis (one-way ANOVA) showed excellent agreement of the analytical data sets generated from the two mass spectrometric detections. The characterization methods have also been satisfactorily applied in an Asia-Pacific Metrology Program (APMP) interlaboratory comparison study. Both the GC–HRIDMS and GC–IDMS/MS methods proved to be sufficiently reliable and accurate for certification purpose. The certified value of cypermethrin in dry mass fraction was 148 μg kg⁻¹ and the associated expanded uncertainty was 14 μg kg⁻¹. The uncertainty budget was evaluated from sample in homogeneity, long-term and short-term stability and variability in the characterization procedure. GLHK-11-01a is primarily developed to support the local and wider testing community on need basis in quality assurance work and in seeking accreditation.     

Evaluation of behavioral differences between native polycyclic aromatic hydrocarbons and (13)C-labeled internal standards during clean-up steps of analysis.

We confirmed that concentrations of polycyclic aromatic hydrocarbons (PAHs) obtained by isotope dilution mass spectrometry (IDMS) using the corresponding (13)C-labeled internal standards are reliable even after clean-up steps. Change in the ratio of phenanthrene to (13)C(6)-phenanthrene was less than 0.2%, although the recovery yield of (13)C(6)-phenanthrene decreased to 60%. Since changes in the ratios were commonly within the relative standard deviations of the concentrations (1.5 - 5.4%) obtained using gas chromatography-mass spectrometry in combination with pressurized-liquid extraction, concentrations obtained by IDMS with (13)C-PAHs should be reliable.     

A simple, practical methodology for routine VSMOW/SLAP normalization of water samples analyzed by continuous flow methods

Normalization of stable isotope data is important for meaningful inter-laboratory comparisons of data, especially for waters where there may be large natural variations in isotope ratios of oxygen and hydrogen. As a result, large, systematic errors may arise in continuous flow applications without correction, whereas normalization to the VSMOW/SLAP scale can facilitate inter-laboratory comparison and can be accomplished by a simple procedure in which secondary laboratory standards, carefully calibrated, are analyzed along with unknown samples. Delta values for these standards, as analyzed, are plotted against the calibrated values and a linear regression is performed. The resulting equation is applied to unknown samples to achieve the normalization. The one-sigma [1sigma] standard deviation for replicate samples by this normalization method using a Finnigan Gasbenchll should be 相似文献