Optimization of the liquid scintillation counting technique for the European interlaboratory comparison on gross α/β activity concentrations in water

A liquid scintillation counting (LSC) measurement method optimization for the gross α/β activity analysis in drinking waters with different chemical and radionuclide composition was performed. The optimized method was suitable to provide gross radioactivity results in drinking waters with the levels of the accuracy and precision similar to those obtained using other radioactivity screening techniques. Robust LSC results contributed to the calculation of gross α/β activity reference values of EC-JRC interlaboratory comparison water samples in 2012. Some of the most common errors in the determination of the gross radioactivity using the LSC are presented.

     

Liquid chromatography-accurate radioisotope counting and microplate scintillation counter technologies in drug metabolism studies

The present study involves an analysis of the performance of liquid chromatography (LC)-accurate radioisotope counting (ARC) and microplate scintillation counter (TopCount) technologies in drug metabolism studies. For the purpose of evaluating these systems, biological samples resulting from the metabolism of a radiolabeled [14C] compound, known as compound B, are analyzed using LC-ARC and TopCount under similar high-performance LC conditions. Counting efficiency is 83% for LC-ARC, 77% for TopCount, and linearity is R2 of 0.9998 versus 0.9984, respectively. The limit of detection for LC-ARC is 12 disintegrations per minute (dpm) with 1-min/fraction counting, yet for TopCount it is 8.7 dpm with 5-min/fraction counting. Under optimal conditions for each, the total run time of LC-ARC is approximately half that of TopCount. These results indicate that there is no significant difference between these two systems in terms of efficiency, linearity, and limit of detection. However, the LC-ARC system does not involve any manual operations, yet TopCount requires manual sample transfer and data import. This study shows that impressive progress has been made in the technology of radioisotope counting in drug metabolism using LC-ARC. This system enhances the resolution of radiochromatograms and is able to measure volatile metabolites that TopCount cannot detect at all. The ability to acquire mass spectra online is also a major advancement. The overall results suggest that the combination of LC-ARC with radioactivity detection and mass spectrometry has great potential as a powerful tool for radioisotope measurement in metabolite identification studies during drug discovery and development.     

Two-dimensional liquid chromatography/mass spectrometry set-up for structural elucidation of metabolites in complex biological matrices

For absorption, distribution, metabolism and excretion (ADME) studies of drug candidates, mass spectrometry (MS) has become an indispensable tool for the characterization of biotransformation pathways. Samples from in vivo animal studies such as plasma, tissue extracts or excreta contain vast amounts of endogenous compounds. Therefore, the generation of metabolite patterns requires dedicated sample pre-treatment and sophisticated separation methods. Methodologies used for metabolite separation are often inappropriate for structure elucidation. Therefore, a two-dimensional liquid chromatography (LC) approach in combination with MS was developed. Study samples were analyzed using high-performance liquid chromatography (HPLC) for the generation of a qualitative and quantitative metabolite pattern (first dimension) with high reproducibility and recovery without extensive sample pre-treatment. Selected radioactive metabolite fractions were then applied to micro-HPLC with off-line radioactivity monitoring and subsequent MS detection (second dimension). Applying the two-dimensional HPLC/MS approach not only major metabolites could be identified, even minor and trace metabolites were characterized. The usage of sampled metabolite fractions allowed also the re-analysis of specific metabolites for additional investigations (e.g. H/D exchange experiments or product ion scanning experiments). It could be clearly shown that the two-dimensional HPLC/MS approach showed mass spectra with higher sensitivity and selectivity significantly improving the characterization of minor and trace metabolites in in vivo ADME studies.     

Alpha-beta discrimination liquid scintillation counting for uranium and its daughters

Advances in liquid scintillation counting (LSC) technologies, such as imporved scintillation cocktail formulations and alpha-beta radiation discrimination, make LSC suitable for applications in uranium process chemistry. Ease of use, low cost, and the huge dynamic range of LSC are distinct advantages for analytical support of actinide processing. All uranium isotopes decay primarily with alpha radiation emission. The immediate short-lived daughters of²³⁸U are²³⁴Th and²³⁴Pa. These nuclides are beta emitters having energy bands that overlap the uranium bands in a liquid scintillation spectrum. The resolution of these overlapping bands by alpha-beta radiation discrimination is useful for uranium quantification and purity verification. Protactinium-234 is a high-energy beta emitter that can be further identified and quantified from it's Cherenkov radiation. Energy spectra were collected on the Packard 2500AB liquid scintillator analyzer for uranyl solutions in diisopropylnaphthalene and pseudocumene based scintillator cocktails. Calibration curves were prepared for nitric, hydrochloric, and sulfuric acid media. Base titrations demonstrated the effect of acid quenching on those system. Ion exchange and water soluble polymer extraction studies are readily followed using liquid scintillation methods.     

Determination of Fe-55 and Ni-63 using semi-preparative ion chromatography – a feasibility study

 The feasibility of semi-preparative high-performance ion chromatography (HPIC) for the analysis of the activation products Fe-55 and Ni-63 in samples of different sources was studied. A mixed anion/cation exchanger column was applied to the separation of Fe(III), Ni(II) and Co(II) using 1 mmol/L PDCA-solution as an eluent. After fractionation of the eluate, Fe(III)- and Ni(II)-fractions were analysed by low-level liquid scintillation counting (LSC). The method was applied to the analysis of corrosion products originating from the primary circuit of a shut-down nuclear power plant. The limits of detection are dependent on the loading of metal ions on the column and are therefore given in terms of specific activities. For a typical sample composition they were found to be 0.011 Bq per mg Fe for Fe-55 and 0.054 Bq per mg Ni for Ni-63. An assessment of semi-preparative HPIC connected to off-line and on-line LSC as compared with standard radiochemical procedures is given. Received: 10 May 1996 / Revised: 2 July 1996 / Accepted: 6 July 1996     

Metabolite analysis,isolation and purity assessment using various liquid chromatographic techniques combined with radioactivity detection

During the discovery of metabolic routes of a drug candidate, radioactively labeled substances are administered. This study reports the multidimensional application of overpressured layer chromatography (OPLC) and high-performance liquid chromatography (HPLC) coupled with online or off-line nondestructive radioactivity detection methods in metabolism studies. Among these methods, digital autoradiography and flow-cell radioactivity detectors (RD) using solid scintillators are used. In this study, the hyphenation of OPLC with RD is reported. The application of the OPLC-RD technique is demonstrated on a metabolism study as well as the multidimensional chromatographic selectivity using normal-phase OPLC for the separation in the first dimension, followed by reversed-phase HPLC-RD, which provides additional selectivity to the separation. Information regarding the identity of radiolabeled metabolites and data obtained from spectroscopic methods could be advantageously used during structure elucidation.     

Gross alpha/beta analyses in water by liquid scintillation counting

Summary The standard procedure for analyzing gross alpha and gross beta in water is evaporation of the sample and radioactivity determination of the resultant solids by proportional counting. This technique lacks precision, and lacks sensitivity for samples with high total dissolved solids. Additionally, the analytical results are dependent on the choice of radionuclide calibration standard and the sample matrix. Direct analysis by liquid scintillation counting has the advantages of high counting efficiencies and minimal sample preparation time. However, due to the small sample aliquants used for analysis, long count times are necessary to reach required detection limits. The procedure proposed consists of evaporating a sample aliquant to dryness, dissolving the resultant solids in a small volume of dilute acid, followed by liquid scintillation counting to determine radioactivity. This procedure can handle sample aliquants containing up to 500 mg of dissolved solids. Various acids, scintillation cocktail mixtures, instrument discriminator settings, and regions of interest (ROI) were evaluated to determine optimum counting conditions. Precision is improved and matrix effects are reduced as compared to proportional counting. Tests indicate that this is a viable alternative to proportional counting for gross alpha and gross beta analyses of water samples.     

Biomedical applications of accelerator mass spectrometry-isotope measurements at the level of the atom

Accelerator mass spectrometry (AMS) is a nuclear physics technique developed about twenty years ago, that uses the high energy (several MeV) of a tandem Van de Graaff accelerator to measure very small quantities of rare and long-lived isotopes. Elements that are of interest in biomedicine and environmental sciences can be measured, often to parts per quadrillion sensitivity, i.e. zeptomole to attomole levels (10(-21)-10(-18) mole) from milligram samples. This is several orders of magnitude lower than that achievable by conventional decay counting techniques, such as liquid scintillation counting (LSC). AMS was first applied to geochemical, climatological and archaeological areas, such as for radiocarbon dating (Shroud of Turin), but more recently this technology has been used for bioanalytical applications. In this sphere, most work has been conducted using aluminium, calcium and carbon isotopes. The latter is of special interest in drug metabolism studies, where a Phase 1 adsorption, distribution, metabolism and excretion (ADME) study can be conducted using only 10 nanoCurie (37 Bq or ca. 0.9 microSv) amounts or less of 14C-labelled drugs. In the UK, these amounts of radioactivity are below those necessary to request specific regulatory approval from the Department of Health's Administration of Radioactive Substances Advisory Committee (ARSAC), thus saving on valuable development time and resources. In addition, the disposal of these amounts is much less an environmental issue than that associated with microCurie quantities, which are currently used. Also, AMS should bring an opportunity to conduct "first into man" studies without the need for widespread use of animals. Centre for Biomedical Accelerator Mass Spectrometry (CBAMS) Ltd. is the first fully commercial company in the world to offer analytical services using AMS. With its high throughput and relatively low costs per sample analysis, AMS should be of great benefit to the pharmaceutical and biotechnology industries as well as other life science areas.     

Assessment of drinking water radioactivity content by liquid scintillation counting: set up of high sensitivity and emergency procedures

In our institute, different procedures have been developed to measure the radioactivity content of drinking water both in normal and in emergency situations, such as those arising from accidental and terrorist events. A single radiometric technique, namely low level liquid scintillation counting (LSC), has been used. In emergency situations a gross activity screening is carried out without any sample treatment by a single and quick liquid scintillation counting. Alpha and beta activities can be measured in more than one hundred samples per day with sensitivities of a few Bq/L. Higher sensitivity gross alpha and beta, uranium and radium measurements can be performed on water samples after specific sample treatments. The sequential method proposed is designed in such a way that the same water sample can be used in all the stages, with slight modifications. This sequential procedure was applied in a survey of the Lombardia district. At first tap waters of the 13 largest towns were examined, then a more detailed monitoring was carried out in the surroundings of Milano and Lodi towns. The high sensitivity method for the determination of uranium isotopes was used to check the presence of depleted uranium in Lake Garda. Reduced equipment requirements and relative readiness of radiochemical procedures make LSC an attractive technique which can also be applied by laboratories lacking specific radiochemistry facilities and experience.     

Monitoring radioactive compounds in high-performance liquid chromatographic eluates: fraction collection versus on-line detection

This study compared two methods of monitoring radioisotopes in high-performance liquid chromatographic eluates (on-line radioactivity detector versus fraction collection and counting). Testing was accomplished by pumping solutions of tritiated water in acetonitrile--water mixture through the detector or to the fraction collector. At most solvent compositions, the detector's counting efficiency and detection limits were poorer than those of the scintillation counter. However, the reproducibility of the detector data was superior at acetonitrile concentrations of less than 50%. This was attributed to the difficulty in collecting fractions of small equal volumes at the lower organic solvent concentrations in short time intervals. We conclude that on-line monitoring with homogeneous detection is the preferred method for detecting radiolabeled compounds in high-performance liquid chromatographic eluates.     

Direct LSC method for determination of bio-origin by C-14 measurement

The aim of the research was to test the generalized direct liquid scintillation spectrometry (LSC) method for bio-origin determination by measurement of C-14. Examples of diversified items with known and unknown bio-origin were measured by liquid scintillation counting and analyzed by procedures, developed for fuel samples. Bio-origin of fuels, lubricants and monomer resins were successfully determined via direct LSC method after simple sample preparation with acceptable accuracy and trueness despite their diversity in color, viscosity, density or chemical composition.

     

Comparison of three methods for measuring 222Rn in drinking water

Three techniques were used to measure ²²²Rn in drinking water: the degassing method followed by counting in an ionisation chamber (IC); gamma spectrometry (GS); and liquid scintillation counting (LSC). Environmental samples were measured in the field using the IC, and the same samples were measured in the laboratory using GS and LSC. The results obtained using the three techniques are compared and discussed in the context of the new Euratom Drinking Water Directive (2013/51/Euratom), which sets out general principles for monitoring radioactive substances such as radon.

     

Feasibility study of an analytical method for detecting <Superscript>90</Superscript>Sr in soil using DGA resin and Sr resin

This study investigated an analytical method for detecting ⁹⁰Sr in soil samples for the routine monitoring of environmental radioactivity. Mineral acid leaching and fusion methods were first used to digest the soil sample, and the analytical results were compared. DGA resin was employed to separate ⁹⁰Y, being a daughter of ⁹⁰Sr. Then, ⁹⁰Y was analyzed by liquid scintillation counter (LSC). These analytical results were compared with those obtained using Sr resin, which is a well-known, simple and reliable separation method. With the DGA resin approach a minimum detectable activity of ~0.28 Bq kg^?1 was detected in a 50 g sample, with 180 min of counting time, 70% recovery and ~97% counting efficiency using a LSC.     

Extraction method and thin-layer chromatographic system for the determination of alpha-l-acetylmethadol and metabolites in biological fluids.

An extraction method and thin-layer chromatographic (TLC) system for the determination of alpha-l-acetylmethadol and its known metabolites (methadol, noracetylmethadol, dinoracetylmethadol, normethadol, 6-acetamide-4,4-diphenyl-3-heptanol, and N-methyl-6-acetamido-4,4-diphenyl-3-heptanol) are described. The parent drug and metabolites are extracted from biological fluids with ethyl acetate and separated by TLC using silica gel plates and a developing system of ethyl acetate-methanol-water-ammonia (85:10:1:1). This system may be used to quantitatively determine levels of radiolabeled drug and metabolites by scraping the TLC plates into 3-mm zonal fractions and measuring the amount of radioactivity by scintillation counting. A representative radiochromatogram obtained from an extract of monkey urine is shown.     

Endocrine-disrupting nonylphenols - ultra-trace analysis and time-dependent trend in mussels from the German bight

A very sensitive and efficient analytical procedure is presented for the determination of 4-nonylphenols (NP) in blue mussels by use of off-line coupling of high-performance liquid chromatography (HPLC) and gas chromatography with mass spectrometric detection (GC-MS). Combined steam distillation and solvent extraction were used to extract the analytes from the mussel samples. Before quantification by GC-MS the raw extracts were purified by normal-phase HPLC. 4-n-Nonylphenol was used as internal standard. The detection limit was 15 ng NP absolute, calculated from the blank value. The method was applied to the determination of NP in blue mussel samples from the German North Sea sampled over a period of 10 years. Collection, homogenization, and storage of the mussels were performed according to the Standard Operating Procedures of the German Environmental Specimen Bank since 1985. The total NP concentrations in the mussels decreased significantly from 1985 (4 microgram kg (-1)) to 1995 (1.1 microgram kg (-1)).     

Determination of one-dimensional distribution of14C-labelled compounds

Three methods of determination of one-dimensional distribution of¹⁴C-labelled compounds are compared: measurement with position-sensitive detector /LB 282/511/, liquid scintillation counting /LSC/, and autoradiography with densitometric quantification. For a mutual comparison of these methods samples of blood serum were used, in which the fractional esterification rate /FER/ was determined by means of LCAT Test. The agreement of the methods of FER determination on the basis of the measurement with LB 282/511 or LSC was checked. In the case of autoradiography a correction for non-linearity between the blackening and the number of -particles striking the area unit was necessary.     

Radiochemical analyses of radiologically-contaminated soil samples in support of transport modeling

In 1951, unsaturated prairie soil was contaminated with fission products and actinides. Fifty years later, in 2001, soil samples were collected from the contaminated site. This paper describes the techniques used to analyze these samples, including gamma-spectroscopy (GS) for ¹³⁷Cs, neutron activation analysis (NAA/GS) for ²³⁸U, liquid scintillation counting (LSC) for ⁹⁰Sr and inductively coupled plasma mass spectroscopy (ICP-MS) for ²³⁸U and ^113mCd. As expected, ICP-MS was found to have the lowest detection level, while the techniques were ranked in order of increasing uncertainty as GS, NAA/GS, ICP-MS and LSC.     

Fast screening of operational aqueous samples by gross alpha and beta counting with LSC systems

At nuclear installations a large number of samples is used to control operational tasks and health physics parameters. A fast screening process can be applied to provide immediate indication on possible contamination, and liquid scintillation counting (LSC) is the preferred method. Many LSC systems, which do not perform pulse shape analysis, are still in use. A screening procedure for these systems is presented based on three windows analysis. It may greatly reduce work and time, compared to using a proportional counter system, besides providing more accurate results.     

抗胆碱能药物曲司氯铵分析方法进展

曲司氯铵是一种抗胆碱能药物,用于治疗膀胱过度活动症引起的尿频和尿失禁.曲司氯铵较其它药物耐受性更高,病人使用更为安全,但其检验方法报道不多.对曲司氯铵的分析方法(包括滴定法、紫外分光光度法、高效液相色谱法、气相色谱法、液体闪烁计数法等)进行了评述和展望.     

Radiochemical methodologies applied to determination of zirconium isotopes in low-level waste samples from nuclear power plants

The ⁹³Zr determination in low-level radioactive wastes generated at nuclear power plants is an important issue for waste disposal purpose. This paper describes an analytical methodology developed for ⁹³Zr determination based on selective separation using extractive resins associated with inductively coupled plasma mass spectrometry (ICP-MS) and liquid scintillation counting (LSC) measurements. The ⁹³Zr results obtained for waste samples were in a good agreement for both techniques and the detection limits of 0.045 μg L^?1 and 0.05 Bq L^?1 were obtained for ICP-MS and LSC techniques respectively.