Isobaric Interferences Research Articles

Titanium Isotope Analysis of Igneous Reference Materials using a Double‐spike MC‐ICP‐MS Method

AbstractTi separation was achieved by ion‐exchange chromatography using Bio‐Rad AG 1‐X8 anion‐exchange and DGA resins. For high‐Fe/Ti and high‐Mg/Ti igneous samples, a three‐column procedure was required, whereas a two‐column procedure was used for low‐Fe/Ti and low‐Mg/Ti igneous samples. The Ti isotopes were analysed by MC‐ICP‐MS, and instrumental mass bias was corrected using a 47Ti‐49Ti double‐spike technique. The 47Ti‐49Ti double‐spike and SRM 3162a were calibrated using SRM 979‐Cr, certificated value 53Cr/52Crtrue = 0.11339. Isobaric interference was evaluated by analysing Alfa‐Ti doped with Na, Mg, Ca, and Mo, and results indicate that high concentrations of Na and Mg have no significant effect on Ti isotope analyses; however, Ca and Mo interferences lead to erroneous δ49/47Ti values when Ca/Ti and Mo/Ti ratios exceed 0.01 and 0.1, respectively. Titanium isotopic compositions were determined for 12 igneous reference materials, BCR‐2, BHVO‐2, GBW07105, AGV‐1, AGV‐2, W‐2, GBW07123, GBW07126, GBW07127, GBW07101, JP‐1, and DTS‐2b. Samples yield δ49/47Ti (‰) of −0.035 ± 0.022, −0.038 ± 0.031, 0.031 ± 0.022, 0.059 ± 0.038, 0.044 ± 0.037, 0.000 ± 0.015, 0.154 ± 0.044, −0.044 ± 0.018, 0.010 ± 0.022, 0.064 ± 0.043, 0.169 ± 0.034, and −0.047 ± 0.025 (relative to OL‐Ti, ±2SD), respectively; of which isotopic compositions of DTS‐2b, JP‐1, GBW07101, GBW07105, GBW07123, GBW07126, and GBW07127 are reported for the first time. Standard Alfa‐Ti was analysed repeatedly over a ten‐month period, indicating a reproducibility of ±0.047 (2SD) for δ49/47Ti, similar to the precisions obtained for geochemical reference materials.

The impact of seasonal and event-based infiltration on transition metals (Cu, Ni, Co) in tropical cave drip water.

The first-row transition metals Cu, Ni, and Co show a strong binding affinity to natural organic matter. Compared to dissolved elements and stable water isotopes, they may be transported rapidly through the soil and host rock into caves in response to infiltration events. This study aims to assess the potential of transition metal ratios as indicators for infiltration changes in response to the seasonal and/or event-based rainfall variation. We developed a protocol to analyze Cu, Ni, and Co in the cave drip water using collision cell ICP-QMS without extensive sample pretreatment. The high Ca matrix leads to significant isobaric interferences on all isotope masses. Our method includes a correction of these matrix effects and yields results with comparable accuracy and reproducibility to other published methods. We applied this protocol to drip water samples from Larga Cave (Puerto Rico) covering at least two full annual cycles between 2014 and 2019 on a bimonthly scale. The analysis of external reference materials yielded a reproducibility between 4.7% and 9.2% (relative standard deviation), validating the accuracy of the matrix correction method. The limit of detection is <0.04 ppb for Cu, <0.02 ppb for Ni, and <0.008 ppb for Co. The analysis of drip water samples from Larga Cave reveals pronounced changes of several orders of magnitude in all Element (El) to Ca, Cu/Ni, and Cu/Co ratios in response to seasonal infiltration changes. In addition, we observe a partly even stronger response after major tropical storms and heavy precipitation events of the period of record, for example, tropical storm "Bertha" (2014) and the category 5 hurricanes "Irma" and "Maria" (both 2017). Transition metal ratios can be accurately measured in cave drip waters with high Ca matrix. At our tropical site, these are promising tracers of infiltration changes in response to changes in the amount of rainfall, providing the first step toward tropical cyclone reconstruction using trace elements in speleothems.

Resolving isobaric interferences in direct infusion tandem mass spectrometry.

RationaleThe co‐fragmentation of precursors in direct infusion (DI) tandem high‐resolution mass spectrometry (HRMS) can complicate the fragment spectra and consequently lead to false hits during compound identification.MethodsThe method herein described, termed IQAROS (incremental quadrupole acquisition to resolve overlapping spectra), modulates the intensities of precursors and fragments by stepwise movement of the quadrupole isolation window over the mass‐to‐charge (m/z) range of the precursors. The modulated signals are then deconvoluted by a linear regression model to reconstruct the fragment spectra with less interference. The hardware to demonstrate the use of IQAROS was an orbitrap with electrospray ionization (ESI) or secondary electrospray ionization (SESI), although the method can also be applied to other ionization techniques or mass analyzers.ResultsAssessing the performance of IQAROS with isobaric standards revealed that the reconstructed fragment spectra match with spectra acquired from the pure standards and that more compounds were correctly identified compared with the classical approach with the quadrupole centered at the m/z value of the precursor of interest. Moreover, the strength of IQAROS is exemplified by the identification of two isobaric biomarkers directly from a breath sample with SESI‐HRMS.ConclusionsWith IQAROS, cleaner fragment spectra of co‐fragmenting isobars during DI‐HRMS analysis can be obtained. IQAROS can easily be set up by the standard graphical user interface of the instrument. Therefore, it facilitates the characterization of features of interest in samples analyzed by DI‐HRMS, for example, in high‐throughput or real‐time metabolomics.

Actinide imaging in environmental hot particles from Chernobyl by rapid spatially resolved resonant laser secondary neutral mass spectrometry

Radioactive particles, so-called hot particles, are of great importance in the risk assessment of environmental pollution and human health hazards. Since most of these particles are only a couple of micrometers in size and thus have correspondingly small atomic inventory, information on origin and composition is difficult to obtain. Many analytical methods do not give insight into isotopic details or require the complete use up of the particle. Resonant laser secondary neutral mass spectrometry (rl-SNMS) has been proven to be a well-suited method for quasi-non-destructive analysis of trace elements. The technique provides high suppression of isobaric interferences and high spatial resolution without necessitating extensive chemical preparation. To measure multiple elements, it is often necessary to switch between laser excitation schemes, requiring elaborate adaptation of the laser setup. Here we present a novel rL-SNMS system capable of multi-element measurements in short succession without any manual adjustment to the laser system. For demonstration, ten micrometer sized hot particles from the Chernobyl Exclusion Zone are analyzed and the obtained isotopic ratios of uranium, plutonium and americium are discussed.

SIMS Analysis of Thin EUV Photoresist Films.

This study reports on the application of secondary ion mass spectrometry (SIMS) for examining thin (20-50 nm) chemically amplified resist films on silicon. SIMS depth profiling was carried out using a gas cluster ion beam to ensure minimal sputter-induced damage to the organic constituents of interest. Specific attention concerned the distribution of the photo acid generator (PAG) molecule within these films, along with the photo-induced fragmentation occurring on extreme ultra-violet photo exposure. Positive secondary ion spectra were collected using a traditional time of flight (ToF)-SIMS and the latest generation IONTOF Hybrid SIMS instrumentation equipped with an OrbitrapTM mass analyzer. Tandem mass spectrometry (MS/MS) capability within the OrbitrapTM secondary ion column was utilized to verify that the C19H17S+ secondary ion did indeed have the molecular structure consistent with the PAG structure. The superior mass resolving power of the OrbitrapTM mass analyzer (∼20× of the ToF mass analyzer) along with improved mass accuracy (a few ppm) proved pivotal in the mass spectral and depth profile analysis of these films. This was not the case for the ToF-SIMS experiments, as the mass spectra, as well as the associated depth profiles, exhibited severe molecular (isobaric) interferences.

Implementation of orbitrap mass spectrometry for improved GC-MS target analysis in lithium ion battery electrolytes

The implementation of orbitrap mass spectrometry for target analysis of volatile species in aged lithium-ion batteries was performed in a case study on butyl carbonates. In comparison to previously applied single quadrupole-based methods, major improvements were obtained.•Sensitivity was improved by effectively background free extracted ion chromatograms of identified marker fragment ions.•Typical isobaric interferences of typical carbonate fragment ions e.g. caused by column bleeding were identified and false positive identification avoided.•Analysis of isotope labeled electrolytes was optimized regarding mass spectrometric data reliability with mass accuracies <0.5 ppm and mass resolutions >100,000.

Eliminating Mo isobaric interference using O2 as reaction gas for Tc measurement by triple quadrupole ICP-MS

The introduction of O2 for the elimination of Mo interference for Tc measurement by ICP-MS/MS.

Differential mobility spectrometry improves uranium isotope ratio measurements on an ion trap mass spectrometer

The characterization of uranium and other radionuclides is important to programs in nuclear forensics. Commonly, isotope-ratio mass spectrometry (IRMS) is employed as a laboratory-based system for quantification of isotope ratios (IR) to shed light on the degree of processing. Transporting nuclear material from the field to the laboratory is problematic while laborious sample processing and long analysis times make IRMS less amenable to real-time measurement. Because size, weight, and power (SWaP) requirements make conventional IRMS difficult to implement for on-site applications, it is attractive to develop IR analysis on an ion trap mass spectrometer which is amenable to field portability. A hindrance to in situ analysis includesmatrix interferences which are best handled by some separation method. Notably, ion mobility instruments have been commonly demonstrated in field use, and, in particular, differential mobility spectrometry (DMS) is a promising companion separation technique to ion traps. DMS enables tunable filtration prior to ion trap MS analysis, removing chemical interferences to address the heterogeneous nature of radionuclides and fission products. DMS may be particularly useful for removing molecular isobaric interferences and, as such, pairing DMS with ion trap MS has potential for fieldable IR analysis. Herein, DMS was coupled to a linear ion trap (LIT) for pre-filtration of uranyl ion (UO2+) from chemical background produced from nano electrospray ionization. Subsequently, isotopic analysis was conducted on the uranyl ion. The 235U/238U ratio measured with the DMS-MS system showed improved signal-to-background, compared to MS alone. Pairing DMS to LITMS improves the accuracy of the MS, while precision of the MS appears to be limited by the precision of the LIT. After DMS filtration, the isotope ratio measurement of 235U/238U decreased from 0.00913 to 0.00713, with the standardized uncertainty improving from 26.58% to 7.21%. Such results indicate that DMS may generally impart greater confidence of nuclear IRMS measurements.

New horizons in microparticle forensics: Actinide imaging and detection of 238Pu and 242mAm in hot particles.

Micrometer-sized pollutant particles are of highest concern in environmental and life sciences, cosmochemistry, and forensics. From their composition, detailed information on origin and potential risks to human health or environment is obtained. We combine secondary ion mass spectrometry with resonant laser ionization to selectively examine elemental and isotopic composition of individual particles at submicrometer spatial resolution. Avoiding any chemical sample preparation, isobaric interferences are suppressed by five orders of magnitude. In contrast to most mass spectrometric techniques, only negligible mass is consumed, leaving the particle intact for further studies. Identification of actinide elements and their isotopes on a Chernobyl hot particle, including 242mAm at ultratrace levels, proved the performance. Beyond that, the technique is applicable to almost all elements and opens up previously unexplored scientific applications.

Gas-phase ion-molecule interactions in a collision reaction cell with triple quadrupole-inductively coupled plasma mass spectrometry: Investigations with N2O as the reaction gas

Nitrous oxide (N2O) was used as a reaction gas to investigate the gas-phase ion-molecule interactions using the Agilent 8900 QQQ-ICP-MS. A multi-element standard containing 45 elements, from Be to Pb, was used for the measurement of ions with QQQ-ICP-MS in the presence and absence of N2O. The main product ion species observed were oxides and nitrides. Comparison of the N2O reaction results with similar measurements conducted with O2 revealed that N2O was more effective at forming oxides in general: The cations Cd+ and Pb+ were shown to produce oxides with N2O where the reaction did not occur with O2. Nitrous oxide was also shown to produce a significant amount of nitride species in a few cases. The general reactivity was shown to be consistent with density functional theory (DFT)-predicted reaction enthalpies, such that all predicted exothermic reactions produced product ions at levels at least 1% of the unreacted ion. Our results show that reaction enthalpy is a reasonable predictor of reactivity with N2O on the timescales of the interactions in non-thermal ICP-MS/MS systems. Our work demonstrates the utility of two relatively new platforms (commercial elemental ICP-MS/MS and EMSL Arrows interface to the NWChem program suite), which allows for the study of a large number of elements within a short period. While DFT with the basis sets utilized here is not the most accurate computational method, it is also not computationally expensive and is shown to be suitable for predicting gas phase reactivity in the QQQ-ICP-MS for the majority of ions studied. The ease and rapidity of data collection and DFT calculations has the potential to be very impactful for the identification of targeted reaction chemistries to be leveraged for analytical method development, such as for the inline separation of isobaric interferences from analytes of interest.

A double-spike MC TIMS measurement procedure for low-amount Ca isotopic analysis of limited biological tissue samples.

The application of Ca isotopic analysis in biomedical studies has great potential to identify changes in Ca metabolism and bone metabolism. Reliable measurement of Ca isotope-amount ratios is challenging considering limited Ca amounts and significant procedural blank levels. In this study, Ca purification was performed using the DGA Resin, optimized for low procedural blanks and separation of Ca from matrix elements and isobaric interferences (Na, Mg, K, Ti, Fe, Ba), while maintaining quasi-quantitative recoveries which are sufficient since a 42Ca-48Ca double-spike (DS) was applied. Ca isotopic analysis was performed using multicollector thermal ionization mass spectrometry (MC TIMS). The obtained procedural Ca blank of ≤10ng enables processing of limited Ca amounts down to 670ng. Data reduction of the measured Ca isotope-amount ratios was performed using an in-house developed software solving the DS algorithm. Data quality was improved by extension of equilibration time of the sample-DS mixture and implementation of a normalization strategy for raw isotopic data. The reported δ(44Ca/40Ca)NIST SRM 915a of NIST SRM 915a processed as a sample was found to be 0.01‰ ± 0.08‰ (2 SD, n = 15). Ca isotope-amount ratios of the reference material NIST SRM 1400 (bone ash), NIST SRM 1486 (bone meal), GBW07601 (human hair), and IAPSO (seawater) were in good agreement within uncertainty with literature data. Novel data on additional reference materials for biological tissues (hair) is presented, which might indicate a potential fractionation of Ca incorporated into hair tissue when compared to the blood pool.

Apatite U‐Pb Dating with Common Pb Correction Using LA‐ICP‐MS/MS

Apatite is a ubiquitous accessory mineral in various rocks (e.g., igneous, metamorphic and clastic sedimentary rocks). However, precise and accurate U‐Pb LA‐ICP‐MS dating of apatite is often compromised by high common Pb levels. Among the different common Pb correction methods, the main advantage of the 204Pb correction method is that it does not assume U/radiogenic Pb concordance. However, 204Pb is difficult to measure using ICP‐MS instruments because of the isobaric interference of 204Hg on 204Pb. We overcome this limitation by using a reaction cell sandwiched between two quadrupoles within an ICP‐MS, which can allow the online chemical separation of two different elements. Ammonia reacts efficiently (&gt; 98%) with Hg while isotopes of Pb are not affected. The approach was tested on eight apatite reference materials (McClure Mountain, NW‐1, UWA‐1, Otter Lake, Slyudyanka, MK‐1, Durango and Fish Canyon Tuff) for which there are independent constraints on the U‐Pb crystallisation age, by comparing U‐Pb dating results employing different reaction gas mixes (NH3‐N2O and NH3 only) in two laboratories. Based on the U‐Pb data and SEM analyses on each sample, we can exclude apatite inter‐ and intra‐grain U‐Pb age heterogeneity, except for a c. 4% variability of ages in the Otter Lake sample. Our results show that accuracy and precision for U‐Pb dating are not measurably affected by different reaction gases, and we accurately reproduce ages of numerous independently characterised apatites within 4% of the reference ages, and the age reproducibility is typically better than 2%.

Rapid Analysis of Volatile Phenols from Grape Juice by Immersive Sorbent Sheet Extraction Prior to Direct Analysis in Real-Time Mass Spectrometry (DART-MS).

Poly(dimethylsiloxane)-based thin-film sorbent sheets (SPMESH) have previously been used for parallel headspace (HS) extraction prior to direct analysis in real-time mass spectrometry (DART-MS) for rapid quantitation of odorants in complex matrices. However, HS-SPMESH extraction is poorly suited for less volatile odorants, e.g., volatile phenols. This report describes modifications to the previous SPMESH extraction device, which make it amenable to parallel extraction of low-volatility analytes from multiwell plates under direct immersion (DI) conditions. Optimization and validation of the DI-SPMESH-DART-MS approach were performed on four volatile phenols (4-ethylphenol, 4-ethylguaiacol, 4-methylguaiacol, and guaiacol) of relevance to the quality of grape juices. Negative-ion mode DART-MS spectra showed a series of oxygenated adducts [M + nO - H]- for all analytes, but isobaric interferences could be limited for three of the four analytes by selecting an appropriate MS/MS transition. Signal suppression from nonvolatiles (sugars, acids) could be overcome by a rinse step. DI-SPMESH-DART-MS analysis of 24 samples could be performed in ∼45 min (30 min extraction, 16 min DART analysis) with 0.5-3 μg/L detection limits in aqueous and model juice solutions. In real grape juices (n = 5 cultivars), good accuracy (72-137%) could be achieved for two of the four volatile phenols initially investigated, 4-ethylphenol and 4-ethylguaiacol. However, poor accuracy was observed for guaiacol in some cultivars, and 4-methylguaiacol could not be quantitated due to interferences with other volatile phenols. Despite these limitations, DI-SPMESH-DART-MS/MS may be useful for prescreening a large number of samples prior to more selective conventional analyses.

Determination of Picomolar Titanium in Seawater by Isotope Dilution Multicollector Inductively Coupled Plasma Mass Spectrometry after Mg(OH)2 Coprecipitation.

A new isotope dilution inductively coupled plasma mass spectrometry (ICPMS) method is developed to determine picomolar concentrations of titanium (Ti) in seawater. The method applies Mg(OH)2 coprecipitation to concentrate Ti from seawater, and uses a new 49Ti-47Ti isotope dilution to eliminate the need for separating Ti from seawater Ca, resulting in an isobaric interference-free analysis by high-resolution multicollector ICPMS. The method uses a 1.8 mL seawater sample with a detection limit of 1.6 pmol L-1 that is determined mainly by Ti contamination during sample preparation rather than by ICPMS sensitivity, instrumental Ti background, or isobaric interferences. An oceanographically consistent vertical profile of dissolved Ti in the Sargasso Sea near Bermuda is measured with this method.

High-resolution imaging and identification of biomolecules using Nano-DESI coupled to ion mobility spectrometry

Simultaneous spatial localization and structural characterization of molecules in complex biological samples currently represents an analytical challenge for mass spectrometry imaging (MSI) techniques. In this study, we describe a novel experimental platform, which substantially expands the capabilities and enhances the depth of chemical information obtained in high spatial resolution MSI experiments performed using nanospray desorption electrospray ionization (nano-DESI). Specifically, we designed and constructed a portable nano-DESI MSI platform and coupled it with a drift tube ion mobility (IM) spectrometer-mass spectrometer. We demonstrate imaging of drift time-separated ions with a high spatial resolution of better than ∼25 μm using uterine tissues on day 4 of pregnancy in mice. Collision cross-section measurements provide unique molecular descriptors of molecules observed in nano-DESI-IM-MSI necessary for their unambiguous identification by comparison with databases. Meanwhile, isomer-specific imaging reveals variations in the isomeric composition across the tissue. Furthermore, IM separation efficiently eliminates isobaric and isomeric interferences originating from solvent peaks, overlapping isotopic peaks of endogenous molecules extracted from the tissue, and products of in-source fragmentation, which is critical to obtaining accurate concentration gradients in the sample using MSI. The structural information provided by the IM separation substantially expands the molecular specificity of high-resolution MSI necessary for unraveling the complexity of biological systems.

Interferences and Matrix Effects on Iron Isotopic Composition Measurements by 57Fe-58Fe Double-Spike Multi-Collector Inductively Coupled Plasma Mass Spectrometry; the Importance of Calcium and Aluminum Interferences

Multi-collector inductively coupled plasma mass spectrometers (MC-ICPMS) are widely used for Fe isotope measurements. The latter may be perturbed by interferences (notably from Cr and Ni) and matrix effects (notably from major elements), caused by elements remaining in the samples after purification. We quantified some of these perturbations and our ability to correct them whenever possible, using Thermo Neptune and Neptune Plus MC-ICPMS with a 57-58Fe double-spike mass bias correction. 54Cr and 58Ni isobaric interference corrections were found to be extremely efficient up to Cr/Fe=0.12 and Ni/Fe=0.04 (g/g natural Fe). Matrix effects were found negligible up to at least Na/Fe=175, Mg/Fe=10, K/Fe=1.5, and Mo/Fe=75 (g/g natural Fe). 28Si2+ interference was found negligible up to Si/Fe=50. Finally, we found that calcium and aluminum could cause significant interferences (e.g., 40Ca16O and 27Al2+), for Ca/Fe ≥ 2.5 and Al/Fe ≥ 2.5. The perturbation intensity relative to the Ca/Fe ratio was found dependent on the measurement conditions (plateau width). While working with samples with potentially high calcium or aluminum contents (such as calcite minerals or tests, bones and teeth, or marine samples and crustal rocks), we recommend to carefully take into account Ca and Al while tuning the instrument and checking the measurement accuracy with isotopic standards (i.e., doping the isotopic standard with Ca and Al levels comparable to those of the samples).

Imaging of I, Re and Tc plant uptake on the single-cell scale using SIMS and rL-SNMS

In radioecological studies, there is a significant need for understanding the plant uptake of radionuclides on a cellular level. The present work applies mass spectrometry to image the radionuclide distribution within the cellular structures of plants at varying concentrations. In a first step, plants of Daucus carota and Pisum sativum labelled with iodine and rhenium were examined, at concentrations in the range of 10 mM. Cross sections of several plant parts were imaged by secondary ion mass spectrometry (SIMS) after cryogenation in order to preserve cell structure. In a second step, the distribution of 99Tc in the two plant species was determined. For radiological reasons, a concentration three orders of magnitude lower was used, rendering measurements with SIMS impossible. Therefore, resonant laser secondary neutral mass spectrometry (rL-SNMS) was used for the first time to image 99Tc with suppression of molecular isobaric interferences. The measurement of only about 1010 atoms of 99Tc atoms is demonstrated and the distribution of 99Tc within a single epidermal cell is imaged.

A single column separation method for barium isotope analysis of geologic and hydrologic materials with complex matrices

The increasing significance of barium (Ba) in environmental and geologic research in recent years has led to interest in the application of the Ba isotopic composition as a tracer for natural materials with complex matrices. Most Ba isotope measurement techniques require separation of Ba from the rest of sample prior to analysis. This paper presents a method using readily available materials and disposable columns that effectively separates Ba from a range of geologic and hydrologic materials, including carbonate minerals, silicate rocks, barite, river water, and fluids with high total dissolved solids and organic content such as oil and gas brines, rapidly and without need for an additional cleanup column. The technique involves off-the-shelf columns and cation exchange resin and a two-reagent elution that uses 2.5 N HCl followed by addition of 2.0 N HNO3. We present data to show that major matrix elements from almost any natural material are separated from Ba in a single column pass, and that the method also effectively reduces or eliminates isobaric interferences from lanthanum and cerium.

Resolving Severe Elemental Isobaric Interferences with a Combined Atomic and Molecular Ionization Source-Orbitrap Mass Spectrometry Approach: The 87Sr and 87Rb Geochronology Pair.

Many fields of basic and applied sciences, including geochronology, astronomy, metabolism, etc., rely on the ability of mass spectrometry to obtain isotope ratio measurements having a high degree of certainty. The inability to resolve difficult isobaric interferences plagues certain measurements. A combined atomic and molecular (CAM) ionization source has been interfaced to a high-field Orbitrap mass spectrometer to alleviate severe atomic, isobaric interferences. This work examines the geochronologically significant 87Sr and 87Rb isotope pair. The mass difference between 87Sr and 87Rb is approximately 0.3 mDa, requiring a minimum resolving power (R = m/Δm) of ∼290,000, a value ∼30× higher than available with sector-field elemental mass spectrometers. Under ultrahigh-resolution conditions, Sr isotope ratio accuracy and precision were evaluated using NIST Sr SRM 987, yielding precision values of <0.1% relative standard deviation (RSD) for the major isotopes and a calculated LOD of 2 pg mL-1 (120 fg of Sr for a 60 μL injection). In addition to manipulating the signal transient length, the total number of ions in the electrostatic trap and the 87Sr/87Rb concentration ratio were found to influence resolution. Ultimately, the isotopes were baseline-resolved with a calculated mass resolution of >1.7M. At equal 87Sr and 87Rb intensities, 87Sr/86Sr was measured as 0.71294 (a relative error of only 0.37%) with a precision of 0.097% RSD, clearly reflecting the alleviation of the isobaric interference.

Prospective identification by neonatal screening of patients with guanidinoacetate methyltransferase deficiency

IntroductionGuanidinoacetate methyltransferase (GAMT) deficiency is an inherited metabolic disorder that impairs the synthesis of creatine (CRE). Lack of CRE in the brain can cause intellectual disability, autistic-like behavior, seizures, and movement disorders. Identification at birth and immediate therapy can prevent intellectual disability and seizures. Here we report the first two cases of GAMT deficiency identified at birth by newborn screening (NBS) in Utah and New York. MethodsNBS dried blood spots were analyzed by tandem mass spectrometry (MS/MS) using either derivatized or non-derivatized assays to detect guanidinoacetate (GUAC) and CRE. For any positive samples, a second-tier test using a more selective method, ultra-performance liquid chromatography (UPLC) combined with MS/MS, was performed to separate GUAC from potential isobaric interferences. ResultsNBS for GAMT deficiency began in Utah on June 1, 2015 using a derivatized method for the detection of GUAC and CRE. In May 2019, the laboratory and method transitioned to a non-derivatized method. GAMT screening was added to the New York State NBS panel on October 1, 2018 using a derivatized method. In New York, a total of 537,408 babies were screened, 23 infants were referred and one newborn was identified with GAMT deficiency. In Utah, a total of 273,902 infants were screened (195,425 with the derivatized method, 78,477 with the non-derivatized method), three infants referred and one was identified with GAMT deficiency. Mean levels of GUAC and CRE were similar between methods (Utah derivatized: GUAC = 1.20 ± 0.43 μmol/L, CRE = 238 ± 96 μmol/L; Utah non-derivatized: GUAC = 1.23 ± 0.61 μmol/L, CRE = 344 ± 150 μmol/L, New York derivatized: GUAC = 1.34 ± 0.57 μmol/L, CRE = 569 ± 155 μmol/L). With either Utah method, similar concentrations of GUAC are observed in first (collected around 1 day of age) and the second NBS specimens (routinely collected at 7–16 days of age), while CRE concentrations decreased in the second NBS specimens. Both infants identified with GAMT deficiency started therapy by 2 weeks of age and are growing and developing normally at 7 (Utah) and 4 (New York) months of age. ConclusionsNewborn screening allows for the prospective identification of GAMT deficiency utilizing elevated GUAC concentration as a marker. First-tier screening may be incorporated into existing methods for amino acids and acylcarnitines without the need for new equipment or staff. Newborn screening performed by either derivatized or non-derivatized methods and coupled with second-tier testing, has a very low false positive rate and can prospectively identify affected children.SummaryCerebral creatine deficiency syndromes caused by defects in creatine synthesis can result in intellectual disability, and are preventable if therapy is initiated early in life. This manuscript reports the identification of two infants with GAMT deficiency (one of the cerebral creatine deficiency syndromes) by newborn screening and demonstrates NBS feasibility using a variety of methods.