Kit preparation of153Sm-EDTMP and factors affecting radiochemical purity and stability

A fast kit method was developed for the production of¹⁵³Sm-EDTMP in two steps avoiding the use of nitric acid, evaporation and sterilization of the final solution by autoclave. Methods of analysis for the determination of chemical and radiochemical purity in the radiopharmaceutical solution were established. Factors affecting radiochemical purity and stability of the complex as the molar ratio of EDTMP/Sm, concentration of phosphate buffer and neutralization of EDTMP prior kit preparation were also analyzed. The use of this radiopharmaceutical in rabbits and patients showed selective skeletal uptake.     

Preparation of samarium-153-EDTMP and determination of its radiochemical purity using paper chromatography

Samarium-153-ethylenediaminetetramethylenephosphonate (¹⁵³Sm-EDTMP) has been used to palliate pain resulting from bone cancer. This paper describes the preparation of¹⁵³SmCl₃ from irradiated natural samarium and the ability of¹⁵³Sm to complex with EDTMP in liquid and in freeze-dried forms. The evaluation of radiolabeled EDTMP was done by paper chromatography. A rapid evaluation of free¹⁵³SmCl₃ and¹⁵³Sm-EDTMP was developed using a miniaturized chromatographic system.     

Optimization of the preparation of153Sm-EDTMP using natural samarium targets for clinical use

¹⁵³Sm (specific activity 3.7 to 5.55 GBq/mg) was produced by irradiating natural Sm₂O₃ at a flux of 2.2·10¹³ n·cm⁻²·s⁻¹. Ethylenediaminetetramethylenephosphonate (EDTMP) was synthesised according to a reported method. Complexation was carried out by varying experimental parameters such as mole ratios of metal to ligand, pH, time and temperature of reaction to obtain quantitative yields. The radiochemical purity of the complex was assessed by various analytical techniques including HPLC. In vitro ligand exchange studies were undertaken to ensure suitability of the product for therapy. Biodistribution studies were carried out in Wistar rats and adequate bone uptake, retention and rapid clearance from blood stream were observed.     

Improving the radiochemical purity determination of 123I-labeled metaiodobenzylguanidine

The HPLC method originally applied at the Nuclear Engineering Institute (IEN) for the radiochemical purity determination of ¹²³iodine labeled m-iodobenzylguanidine (¹²³I-mIBG) takes 18.5 min. The final product release also depends on this result, and to facilitate this stage, we aimed to decrease this analysis time. We also intended to use fewer toxic compounds, if feasible. The optimization approach used herein was a combination of factorial and mixture designs to study simultaneously the selected variables. Analysis time, resolution and chromatograms aspect were the measured responses. The qualitative analysis of these responses provided the best chromatographic separation conditions that were 52 mM KH₂PO₄ in a solution of ethanol and water (1:1), applying a flow rate of 0.50 mL min^?1 and C18 column (4.6 × 250 mm, 5 μm). These optimum conditions not only decreased the analysis time in 61 %, but also allowed the reduction of mobile phase toxicity. To assure reliable data, method validation was performed for these conditions. The method has proved its specificity, the detection limit found was 3.70 × 10^?4 MBq mL^?1 and the quantification limit has corresponded to 1.11 × 10^?3 MBq mL^?1. Repeatability and intermediate precision has not exceeded 3 and 5 %, respectively, and the accuracy has matched the interval of 95–105 %. This new method has been routinely applied in the radiochemical purity determination of ¹²³I-mIBG at IEN.     

New techniques in radiochemical determinations using polarographic methods

This work was undertaken as part of a research program on the development of new radio-chemical procedures. The techniques used are those of standard polarographic practices. Radio-isotopes that can be polarographically reduced to the zero oxidation state amalgamate with the mercury, are removed from the solution, and the radioactivity determined. Reproducible curves of activity vs. Ede are found to be in every way analogous to polarograms obtained under the same experimental condition. The requirements necessary for any radio-ihotope to be determined quantitatively by this method are that the radio-isotope be polarographically reduced to the zero oxidation state and that no other radio-isotope be polarographically reduced at the same potential. This type of analysis has been successfully applied to several radio-isotopes and mixtures of radio-isotopes.     

Fast liquid chromatographic determination of radiochemical and chemical purity of [11C]methionine by UPLC technique

Salinity, water logging, high nitrate, fluoride and dissolved uranium concentration in drinking water of southwest Punjab has impacted the local population leading to health issues and additional burden on economy. Though it was known that both U and its daughter products especially Rn contribute to radiological dose to the population through drinking water, there were no correlation studies carried out between these radioactive elements in U impacted regions of southwest Punjab. In this study, an initiative has been taken to assess the doses due to dissolved radon in drinking water. In addition, the U–Rn couple is evaluated in detail along with other hydrochemical parameters. The radon concentration ranges from 360–1700 Bq/m³ for Faridkot and 140–1400 Bq/m³ for Muktsar for both seasons and the related average total dose due to radon for both season of Faridkot and Muktsar are 9.79 µS/year and 7.74 µS/year respectively. The total dissolved uranium is in range of 16–350 µg/L for Faridkot and 14–106 µg/L for Muktsar for both seasons. An inverse correlation was observed between Rn and U, which could be attributed to diverse geochemistry of U and Rn in groundwater.

     

The radiochemical purity determination of18F preparations

A simple and fast chromatographic method for determining the chemical form of¹⁸F is given.     

Multielement radiochemical neutron activation analysis of high purity aluminium

Summary A radiochemical neutron activation analysis technique for the determination of 51 elements in high purity aluminium via medium- and long-lived indicator radionuclides has been developed. It is based on a separation procedure involving the removal of ²⁴Na, produced via the reaction ²⁷Al(n,), on a hydrated antimony pentoxide column and further separation of the radionuclide mixture into 11 groups on two Dowex 1X8 columns and one Dowex 50X8 column from HCl/HF and HCl media as well as the extraction of copper with APDTC in chloroform. The indicator radionuclides for the significant impurities thorium and uranium, ²³³Pa and ²³⁹Np, were separated with satisfactory selectivity in one fraction. For 43 elements, the limits of detection are <10 ng/g, for thorium and uranium, they are 50 pg/g. The method was applied to the analysis of different high purity aluminium samples. For a number of elements, the results of this technique are compared with those of other techniques.

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Radiochemische Multielement-Neutronenaktivierungsanalyse von hochreinem Aluminium

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Dedicated to Prof. Dr. W. Fresenius on the occasion of his 75th birthday     

Effect of aluminium on the radiochemical purity and99mTc-MDP biodistribution

Results on aluminium and^99mTc-MDP interaction under in vivo and in vitro conditions are presented. Aluminium, as chemical impurity, which in^99mTc-eluate some times appears above the allowed concentration (more than 20 g/ml) in the course of preparate labeling procedure may interact under in vitro conditions. Such a form of interaction was discovered by radiochromatographic methods. The highest Al³⁺-ion concentration studied (200 g/ml) increases the^99mTc-hydrolysate content by about ten times compared to the control. However, the same Al³⁺-ion concentration decreases by about four times the content of^99mTc-MDP complex, which is responsible for deposition in bones. According to biodistribution results obtained on wistar rats, significant increase of radioactivity in liver is observed, and at the same time the decrease in bones, in dependence on the aluminium ion dose. With a maximum dose of 200 g Al³⁺/kg b.w. the uptake of^99mTc-MDP in liver was higher for about 35% and lower in bones for 3.6%/g. With compensan (antacide drug) with which the animals were primarily treated per os, only considerably small changes were observed in^99mTc-MDP uptake, if compared to the control group. These findings are very important for clinical application of this preparate.     

Determination of radiochemical purity of chlormerodrin-203 by electrophoretic method

An electrophoretic method to control the radiochemical purity of chlormerodrin-203 is described. Optimum conditions for the separation of inorganic and organically bound mercury-203 were determined by investigating its mobility in the concentration range of 1·10⁻⁵–1·10⁻² M NaCl. Maximum separation, of²⁰³Hg and hydroxychlormerodrin was achieved at 0.05M NaCl, at the potential gradient of 8V/cm for 2 hrs.     

Study on analysis of153Sm-EDTMP stability in vitro and vivo by HPLC

The behavior of¹⁵³Sm-EDTMP in vitro and vivo is analyzed by the size exclusion HPLC. The experimental results show that EDTMP amounts have an obvious effect on the stability in vitro and uptake of¹⁵³Sm-EDTMP in the liver. HPLC analysis of urine sample indicates that¹⁵³Sm-EDTMP es excreted in the original form. The behavior in vivo of¹⁵³Sm-EDTMP containing 4 μg is similar to that of¹⁵³Sm-EDTMP containing 50 μg EDTMP at 1 h post-injection.     

Chemometric quality control of chromatographic purity

It is common practice in chromatographic purity analysis of pharmaceutical manufacturing processes to assess the quality of peak integration combined by visual investigation of the chromatogram. This traditional method of visual chromatographic comparison is simple, but is very subjective, laborious and seldom very quantitative. For high-purity drugs it would be particularly difficult to detect the occurrence of an unknown impurity co-eluting with the target compound, which is present in excess compared to any impurity. We hypothesize that this can be achieved through Multivariate Statistical Process Control (MSPC) based on principal component analysis (PCA) modeling. In order to obtain the lowest detection limit, different chromatographic data preprocessing methods such as time alignment, baseline correction and scaling are applied. Historical high performance liquid chromatography (HPLC) chromatograms from a biopharmaceutical in-process analysis are used to build a normal operation condition (NOC) PCA model. Chromatograms added simulated 0.1% impurities with varied resolutions are exposed to the NOC model and monitored with MSPC charts. This study demonstrates that MSPC based on PCA applied on chromatographic purity analysis is a powerful tool for monitoring subtle changes in the chromatographic pattern, providing clear diagnostics of subtly deviating chromatograms. The procedure described in this study can be implemented and operated as the HPLC analysis runs according to the process analytical technology (PAT) concept aiming for real-time release.     

Assessing chromatographic peak purity using condition index and singular value evolving profiles

A new method for determining chromatographic peak purity is presented. The method uses condition index evolving profiles (CIEPs) and singular value evolving profiles (SVEPs). To produce a CIEP or a SVEP, singular value decompositions are performed on data matrices containing the analyte's pure-component spectrum and sample spectra as they evolve over a chromatographic time profile. Visual inspection of condition indices and singular values as they evolve over time enables detection of less than 0.5% of a spectrally similar impurity with no chromatographic resolution (R_s = 0). Additionally, the CIEPs and SVEPs allow estimation of chromatographic pure regions. This method represents an extension of CIEPs which have been used in successful library searches of multicomponent mixtures based on gas chromatography-Fourier transform infrared spectra and liquid chromatography-UV-visible spectra.     

General principles of enzymatic methods and their use in the determination of the radiochemical purity of mono-and disaccharides labelled with14C

General principles of enzymatic methods for the determination of radiochemical purity of natural¹⁴C-mono-and-disaccharides are suggested, and analytical schemes using these principles have been worked out. The enzymatic method of determining the radiochemical purity of¹⁴C-glucose is given as an illustration.     

Chemical and radiochemical evaluation of the purity of99mTc extracted by MEK

Solvent extraction separation of^99mTc from⁹⁹Mo using methyl ethyl ketone(MEK) has been found to be an effective method of obtaining^99mTc of medicinal purity from low specific activity⁹⁹Mo. The authors have investigated the effect of alkali and molybdenum concentration on the extraction of⁹⁹Mo and^99mTc into methyl ethyl ketone. The possibility of methyl ethyl ketone forming enol and condensation products and its effect on the final extraction efficiency and purity of^99mTc has been studied. Sodium molybdate has been found to have a good salting out effect on^99mTc pertechnetate and hence^99mTc extraction can be better accomplished from low specific activity⁹⁹Mo solutions. The ketone seems to form traces of condensation products in the extraction procedure. These have been found to be coextracted with^99mTc into MEK but did not affect the extractability of^99mTc. It was observed that neutral alumina column removes these condensation products from MEK containing^99mTc. Alternately these could be filtered off by acidification of the final aqueous^99mTc solution. The studies indicate that under optimum experimental conditions methyl ethyl ketone separates^99mTc from⁹⁹Mo with high efficiency and yields^99mTc of high purity suitable for use in nuclear medicine in the form of various labelled compounds.     

Determination of silicon in high purity metals by radiochemical NAA and CPAA

The indicator radionuclide³¹Si produced in neutron and deuteron activation analysis for silicon via the reactions³⁰Si(n,) and³⁰Si(d,p), respectively, is specifically separated from the irradiated sample by distillation as³¹SiF₄. In the case of aluminium, the distillation is carried out from a HF(HNO₃)H₂O₂ medium and in the case of molybdenum, niobium, tantalum, titanium and vanadium from a HF/HNO₃/HBr/H₂SO₄ medium. Using liquid scintillation counting, the achievable detection limits for neutron activation analysis are, depending on the type of the matrix, between 4–50 ng/g, and for the deuteron activation analysis of tantalum the detection limit is 5 ng/g.     

Sample preparation and isolation using planar chromatographic methods

The state of art of the various preparative planar liquid chromatographic (PLC) methods is summarized, especially for off-line and on-line sample application. The sample purification possibilities for PLC techniques are discussed. Purification and isolation strategies using forced-flow planar chromatographic techniques, such as overpressured layer chromatography and rotation planar chromatography, are suggested in the form of flow charts.