Chromatography radiochemical purity

Radiochemical purity determinations consist of separating the different chemical substances containing the radionuclide. The radiochemical purity of labeled pharmaceuticals is typically determined by paper chromatography (paper impregnated with silica gel or silicic acid). The most frequently used radioisotope is technetium-99m obtained by daily elution with saline... 

The product 144 has 98.8% radiochemical purity after chromatography and recrystallization. No kinetic tritium isotope effect and tritium exchange with the solvent in the last two syntheses has been studied. 

Determination of the radiochemical purity using fast protein liquid chromatography (FPLC) and instant thin layer chromatography (ITLC), and purification using the SepPak procedure and size exclusion chromatography. 

High performance liquid chromatography analysis of DOTATATE labelled with the radionuclides under study showed a single peak for each agent. In all cases, the labelling efficiency (radiochemical purity) was found to be greater than 98%. The distribution of radioactivity in selected organs of rats... 

The radiochemical purity of the Rc-HEDP was determined by instant thin layer chromatography (ITLC) using ITLC sihca gel strips developed in 95% acetone. The strips were dried and cut into 0.5 cm long segments, and the radioactivity was measured using a gamma counter (Ecko Electronics). The Re-HEDP remained at the origin (Rj = 0) and the ReO moved to the solvent front (Rf = 0.9). 

Measurement of labelling yield and subsequent radiochemical purity requires a suitable analytical technique, and the method of choice for radio-labelled peptides is reversed phase HPLC with on-line UV and radiometric detection. It is important to use as stringent a separation method as possible with isocratic or slow mobile phase composition gradients over the peptide peak. Ideally, more than one mobile phase system should be used (e.g. a phosphate buffer-methanol system in addition to the standard water-acetonitrile system), since these may show the presence of new impurities. It is important to recognize that HPLC analyses only measure those components that elute from the column. Insoluble, highly lipophilic or positively charged species may bind to the solid phase. It is very important to verify the absence of these species by a complimentary technique such as thin layer chromatography (TLC) and to ensure that the two techniques produce similar results. 

For labelling with temperature, reaction time, pH and molar ratio (peptide/lutetium) were varied with the aim of optimizing labelling efficacy, radiochemical purity and stability. Quahty control procedures included reversed phase HPLC (C18 column) and chromatography on various solvents and/or supports [16.9],... 

F-FMISO is synthesized in one-step reaction between the protected precursor, l-(2/-nitro-l,-imidazolyl)-2-0-tetrahydropyranyl-3-0-toluenesulfonyl-propanediol (NITTP) and 18F-containing Kryptofix 2.2.2 in acetonitrile solution (Kamarainen et al, 2004). The labeled product is hydrolyzed with acid to give 18F-FMISO, which is further purified by column chromatography using a Sep-Pak cartridge. From an automated synthesis, the radiochemical yield is 34% at EOB after a synthesis time of 50 min. HPLC shows a radiochemical purity of 97%. The molecular structure of 18F-FMISO is shown in Fig. 8.2f. 

Radiochemical purity It is determined by the HPLC method or ion pair chromatography. 

Radiochemical purity is analyzed by thin-layer chromatography, described in this book. Poor quality of a radiopharmaceutical would affect the chnical information and cause uimecessary radiation exposure of a patient. 

Thin-layer chromatography (TLC) is commonly used for the determination of radiochemical purity in nuclear medicine. TLC was described as early as 1967 for testing radiopharmaceuticals (Hoye 1967). Since the introduction of TLC (Izmailov and Shraiber 1938 Stahl 1956), a variety of modifications and new applications have been reported (Fairbrother 1984). 

Fig. 9.1.1.1. Determination of the radiochemical purity of a radiopharmaceutical by instant thin-layer chromatography (ITLC) using two different solvents, methyl ethyl ketone (MEK) and saline...

Whatman 3MM is the material of choice for determination of the radiochemical purity by partition chromatography. (For information on materials. Tables 9.1.1.1 and 9.1.1.2.)... 

Procedure for the determination of radiochemical purity by ITLC or paper chromatography ... 

Thin-layer chromatography on silica gel plates offers reliable results faster " Tc-per-technetate migrates with the solvent (saline) front reduced, hydrolized activity remains at the start. The results of radiochemical purity generally exceed 99%. 

Radiochemical Purity. The European Pharmacopeia requires thin-layer chromatography (TLC) (distance 10-15 cm) for the identification of impurities using methylethylke-tone (MEK) as solvent. The radioactivity corresponding to Tc-HSA must not be less than 95% (Council of Europe 2005). 

Paper chromatography (USP) is recommended for the identification of impurities, using 70% methanol as solvent. Free " Tc-sodium pertechnetate is measured at Rf= 0.6, and Tc-MAA is identified at the origin. The radiochemical purity of " Tc-MAA should not be less than 90%. 

Radiochemical Purity. Tc-albumin microcolloid is not described in the European Pharmacopeia. Thin-layer chromatography is recommended by the manufacturer, using 85% methanol as solvent. Free Tc-sodium pertechnetate is measured at Rf 0.7 and... 

Radiochemical Purity. Tc-sestamibi is described in the European Pharmacopeia (Council of Europe 2005). Thin-layer chromatography using reverse-phase silica gel plates (octadecylsilyl-silica gel) and a mixture of acetonitrile, methanol, ammonium acetate, and tetrahydrofuran as solvent system is recommended for the separation of free 99rnTc-sodium pertechnetate (Rf =0.9) and reduced, hydrolized " Tc-activity (Rf=0-... 

The commonly used method is thin-layer chromatography on aluminum oxide-coated plastic TEC plates and absolute ethanol as solvent. Free Tc-sodium pertechnetate and reduced, hydrolized Tc-activity remain at the start. Tc-sestamibi is measured at an Rf of 0.9, moving with the solvent front. The radiochemical purity of Tc-sesta-mibi should not be less than 94%. 

Radiochemical Purity. Tc-Tetrofosmin is not described in the European Pharmacopeia. A rapid instant thin-layer chromatography (ITLC) procedure for determination of the radiochemical purity of Tc-tetrofosmin has been published (Van Hemert et al. 2001). 

Radiochemical Purity. Tc-exametazime is included in the Ph. Eur. (Council of Europe 2005). Thin-layer chromatography on silica gel fiberglass plates using two solvent systems is described to determine the radiochemical purity of the injection solution. Free Tc-Na-pertechnetate (B) is determined in saline, the lipophilic Tc-HMPAO complex (D) is quantified indirectly by a subtraction method (Tab. 1). Previously, three solvent systems had been used, as recommended by the manufacturer. 

Thin-layer chromatography on Gelman silica gel sheets and paper chromatography on Whatman 1 strips is recommended by the manufacturer, using three solvent systems for the analysis of the lipophilic Tc-HMPAO complex (D), the secondary hydrophilic complex (A), unbound " Tc-Na-pertechnetate (B), and reduced, hydrolized " Tc activity (C) (Tab. 2). Since reduced, hydrolized Tc activity is determined separately, each impurity is quantified. The radiochemical purity of lipophilic " Tc-exametazime should not be less than 80% (USP 28). 

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