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Background When using iTLC-SG thin layer chromatography plates to measure radiochemical impurities in 99mTc medronate, falsely high values were obtained for 99mTc pertechnetate impurity. Preliminary investigations indicated that the mass of 99mTc medronate applied to the plate influences the value. Aim The goal of this study was to determine if the concentration of medronate influences the value obtained for 99mTc pertechnetate impurity. Experimental 99mTc medronate was prepared at two concentrations: 4 mg/mL and 0.2 mg/mL. Impurity levels were measured using three stationary phases: dried and undried iTLC-SG and 54SFC paper. Two mobile phases were used: methyl ethyl ketone to detect 99mTc pertechnetate and sodium acetate 136 g/L to detect hydrolysed and colloidal 99mTc. Sample spot drying and volume were also investigated. Results With 4 mg/mL samples, the three stationary phases measured similar impurity levels (p > 0.05). With the 0.2 mg/mL samples, higher levels of 99mTc pertechnetate were measured with iTLC-SG than with paper (p

Background: The rate at which radioactive albumin particles clear from the bloodstream is used to measure reticuloendothelial capacity. Traditionally, iodine radioisotopes have been used. Non-active albumin particles mixed with the technetium-99 m labelled particles of the readily available radiopharmaceutical 99 mTc Albumin Nanocolloid (ANC) would be more convenient. Aim: To prepare human albumin nanospheres (HAN) with a diameter similar to 99 mTc-ANC and to investigate their stability. Experimental: HAN were prepared by heating 30 g/l albumin solution pH 10 at 70°C for 20 min then 75°C for 17.5 min, adjusting to pH 7.5 and sterilizing by filtration. Seven batches were prepared. The HAN diameter was measured by photon correlation spectroscopy at 0–3 months. Various measures of stability were performed. Results: The mean diameter of the HAN was 3.9 ± 1.9, 4.0 ± 1.5, 4.4 ± 1.6 and 4.2 ± 2.0 nm at 0, 1, 2 and 3 months. After mixing HAN and 99 mTc-ANC, no changes in particle size or radiolabelling of ANC were detected. Conclusions: HAN with a diameter comparable to the particles in 99 mTc-ANC were prepared successfully. The diameter of HAN does not change over 3 months or after mixing with 99 mTc-ANC. The particle size and labelling efficiency of 99 mTc-ANC are not affected by the addition of HAN. Copyright © 2011 John Wiley & Sons, Ltd.

OBJECTIVE: To determine whether radiochemical purity is affected when 99mTc radiopharmaceuticals are prepared using sodium chloride injection from plastic ampoules that have been exposed to light. METHODS: Sodium chloride injection from plastic ampoules that were either exposed to light for 7 days or protected from light was used in the preparation of nine common 99mTc radiopharmaceuticals: albumin nanocolloid, exametazime, macrosalb, mebrofenin, medronate, pentetate, sestamibi, succimer and tetrofosmin. Five different batches of ampoules (exposed and unexposed) were used for each radiopharmaceutical. Radiochemical purity was measured by established analytical methods (thin-layer chromatography, liquid chromatography and nuclepore filtration) as specified in the European Pharmacopoeia or by the manufacturer. Analysis was performed within 1 h of preparation and at the products' expiries. RESULTS: The radiochemical purity of each 99mTc radiopharmaceutical was satisfactory when unexposed sodium chloride injection was used in its preparation. There was a significant difference between exposed and unexposed results (P < 0.05) for 99mTc exametazime (69.0 ± 9.3% vs. 88.6 ± 0.8%), 99mTc albumin nanocolloid (94.3 ± 1.1% vs. 98.8 ± 0.4%) and 99mTc macrosalb (84.0 ± 4.1% vs. 98.0 ± 2.2%) after preparation. Unsatisfactory radiochemical purity was the result of 99mTc pertechnetate impurity. The radiochemical purities of 99mTc albumin nanocolloid and 99mTc macrosalb increased over time and were satisfactory at their expiries. CONCLUSION: When 99mTc albumin nanocolloid, 99mTc macrosalb and 99mTc exametazime are prepared using sodium chloride injection from plastic ampoules that have been exposed to light, radiochemical purity is adversely affected. The other 99mTc radiopharmaceuticals tested are unaffected.

Background: The European Pharmacopoeia and radiopharmaceutical manufacturers specify Instant Thin-Layer Chromatography Silica Gel impregnated glass fibre (ITLC-SG) as the stationary phase for measuring the radiochemical purity (RCP) of most technetium-99m (99mTc) radiopharmaceuticals. During 2008, The Pall Corporation stopped manufacturing ITLC-SG. A replacement is required. Aim: To evaluate Varian's Glass Microfibre Chromatography Paper impregnated with salicic acid (GMCP-SA) as a replacement. Experimental: Samples of six 99mTc radiopharmaceuticals (albumin nanocolloid, colloidal tin, exametazime, medronate, pentetate and succimer) were prepared containing levels of radiochemical impurities between 0 and 10%. Samples were tested using ITLC-SG and GMCP-SA with the mobile phase specified in the pharmacopoeia or by the manufacturer. Analysis was performed by thin-layer radiochromatogram scanning. Results: For measuring the RCP of albumin nanocolloid, colloidal tin, exametazime and succimer, GMCP-SA is a suitable replacement for ITLC-SG. For medronate, GMCP-SA is suitable for measuring colloidal 99mTc impurity despite producing slightly higher values than ITLC-SG, but unsuitable for measuring 99mTc pertechnetate impurity due to significant over-estimation. For pentetate, GMCP-SA is suitable for measuring colloidal 99mTc impurity but gives slightly higher values for 99mTc pertechnetate impurity than ITLC-SG. Conclusion: GMCP-SA is a suitable alternative to ITLC-SG for analysing some 99mTc radiopharmaceuticals but is not a universal replacement. Copyright © 2009 John Wiley & Sons, Ltd.

To determine if 99mTc-Nanocoll is affected by storage in a syringe, passage through an R-Lock or mixing with Patent Blue V dye.A Nanocoll kit was reconstituted at 280 MBq/5 ml. Samples of 0.5 ml were drawn into 3 ml Plastipak syringes. After 1 h and 6 h, adsorption of 99mTc on a syringe was measured and the following tests of quality were performed on samples from the kit and a syringe: 99mTc-pertechnetate impurity by thin-layer chromatography, the percentage of 99mTc on particles100 nm by Nuclepore filtration and particle size by photon correlation spectroscopy. These tests were also applied to samples that had been passed through an R-Lock or mixed with Patent Blue V. Each experiment was performed five times.In all samples, adsorption of 99mTc on syringes was1%, 99mTc-pertechnetate impurity was2%,95% of 99mTc was labelled to particles100 nm in diameter, the mean particle diameter was 6.6 nm and the particles had a diameter of12 nm. All tests showed no significant difference (P0.05, n = 5) between 99mTc-Nanocoll from the original kit and a syringe at either 1 h or 6 h. Similar results were obtained with samples that had been passed through an R-Lock or mixed with Patent Blue V.A capped 3 ml Plastipak syringe is a suitable container in which to supply 99mTc-Nanocoll. Neither passage through an R-Lock nor mixing with Patent Blue V affects the quality of 99mTc-Nanocoll.

Routine technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) radiochemical purity measurements have revealed occasional unacceptably low values. Preliminary investigations suggested a causal link with the residence time of sodium chloride injection in the syringe used to reconstitute the MAG3 kit.To investigate the cause of this phenomenon, determine how it can be avoided and establish whether it occurs with other 99mTc radiopharmaceuticals.99mTc-MAG3 was prepared by drawing sodium chloride injection into a lubricated, three-part, 10 ml Plastipak syringe and using it to reconstitute a MAG3 kit immediately or after a 15 min incubation period. The radiochemical purity was measured by high-performance liquid chromatography. The experiment was repeated using lubricant-free, two-part, Norm-Ject syringes and lubricated, two-part, Monoject syringes (15 min incubation only). To investigate the influence of Plastipak's rubber components on the radiochemical purity, samples were prepared using sodium chloride injection that had been incubated with lubricated or lubricant-free rubber plunger ends. Similar experiments were performed to determine the effect of Plastipak on 99mTc-exametazime, 99mTc-sestamibi and 99mTc-tetrofosmin.The radiochemical purities of 99mTc-MAG3 prepared with sodium chloride injection incubated for 0 and 15 min in Plastipak syringes were 96.4+/-0.5% and 89.4+/-5.5%, respectively. The difference was significant (P0.05, n=10). With Norm-Ject syringes, the radiochemical purities were 96.5+/-0.5% and 96.6+/-0.5%, respectively. The difference was not significant (P0.05, n=10). With Monoject syringes, the radiochemical purity was 96.6+/-0.4% (n=10). 99mTc-MAG3 prepared using sodium chloride injection treated with lubricated and unlubricated syringe rubber plunger ends had radiochemical purities of 85.3+/-6.6% and 82.1+/-6.5% (n=5), respectively. The radiochemical purities of other 99mTc radiopharmaceuticals prepared using sodium chloride injection incubated for 0 or 15 min in Plastipak syringes were as follows: 99mTc-exametazime, 95.3+/-0.6% and 94.5+/-1.8%; 99mTc-sestamibi, 98.0+/-0.6% and 97.7+/-0.6%; 99mTc-tetrofosmin, 96.5+/-0.2% and 97.0+/-0.4%. None of the differences was significant (P0.05, n=5).A lipophilic impurity, originating from the rubber plunger of a three-part Plastipak syringe, is formed in 99mTc-MAG3 when the sodium chloride injection used to reconstitute the kit is in the syringe for a prolonged time. The effect is eliminated by using a two-part syringe or by injecting the sodium chloride injection into the kit immediately. The phenomenon does not occur with 99mTc-exametazime, 99mTc-sestamibi or 99mTc-tetrofosmin.

Objectives To simulate 9 0 Y-Zevalin thin-layer chromatograms representing a range of radiochemical purities, to compare the radiochemical purities obtained with five techniques used to quantify 9 0 Y on the plates and tomeasure the reproducibility of the five techniques at the minimum acceptable radiochemical purity of 95%. Methods Yttrium-90 solutions were pipetted onto the origin and solvent front lines of thin-layer chromatography (TLC) plates to simulate radiochemical purities of 90%, 92%, 94%, 95%, 96%, 98% and 100%. Each plate was analysed using three TLC scanners (Bioscan AR2000, Bioscan Mini-scan and an instrument constructed in-house) and two cut-and-count techniques: one using a sodium iodide well detector and the other a liquid scintillation counter. The reproducibility of each technique was measured by analysing the 95% plate 10 times. Results The radiochemical purities measured by the five techniques agreed well. The means of the seven results obtained with each agreed within 0.7%. The reproducibility of each technique was excellent. The coefficient of variation for 10 measurements was ≤ 0.3%. The signal to background ratios were satisfactory, ranging from 24 to 2.1 × 10 5 . Conclusion Each technique is suitable for analysing 9 0 Y-Zevalin TLC plates.

Review(s) of: Saving the souls of medieval London: Perpetual chantries at St Paul's Cathedral, c. 1200-1548, by Rousseau, Marie-Helene, (Church, Faith and Culture in the Medieval West), Farnham, Ashgate, 2011, hardback, pp. 256, 3 b/w illustrations, R.R.P. 65.00 pounds, ISBN 9781409405818.

When using iTLC-SG thin layer chromatography plates to measure radiochemical impurities in (99m) Tc medronate, falsely high values were obtained for (99m) Tc pertechnetate impurity. Preliminary investigations indicated that the mass of (99m) Tc medronate applied to the plate influences the value.The goal of this study was to determine if the concentration of medronate influences the value obtained for (99m) Tc pertechnetate impurity.(99m) Tc medronate was prepared at two concentrations: 4 mg/mL and 0.2 mg/mL. Impurity levels were measured using three stationary phases: dried and undried iTLC-SG and 54SFC paper. Two mobile phases were used: methyl ethyl ketone to detect (99m) Tc pertechnetate and sodium acetate 136 g/L to detect hydrolysed and colloidal (99m) Tc. Sample spot drying and volume were also investigated.With 4 mg/mL samples, the three stationary phases measured similar impurity levels (p 0.05). With the 0.2 mg/mL samples, higher levels of (99m) Tc pertechnetate were measured with iTLC-SG than with paper (p 0.05). Neither sample spot drying nor volume was found to affect impurity levels measured.When using iTLC-SG to measure the radiochemical purity of (99m) Tc medronate, an artefactually high level of (99m) Tc pertechnetate impurity is measured when the medronate concentration in the sample is low. The iTLC-SG stationary phase may be unsatisfactory for measuring the radiochemical purity of (99m) Tc medronate.

OBJECTIVE The longer the time between elutions of a technetium-99m (Tc) generator, the greater the Tc : Tc ratio in the eluate. Information is limited on how this affects the radiochemical purity (RCP) of Tc radiopharmaceuticals. The aim was to determine whether the RCPs of Tc radiopharmaceuticals are affected when prepared using Tc-pertechnetate from a generator that remained uneluted for 7 days. METHODS Eight Tc radiopharmaceuticals were investigated: albumin nanocolloid, macrosalb, medronate, mertiatide, pentetate, sestamibi, succimer and tetrofosmin. Five samples of each were prepared with eluate from a generator that had been previously eluted within 24 h (control). These were compared with five samples adulterated with Tc to replicate the Tc : Tc ratio present in eluate from a generator that has remained uneluted for 7 days (test). The RCP of each sample was measured 1 h after preparation and at the product's expiry. RESULTS Significant differences (P

Review(s) of: Wycliffite controversies. by Bose, Mishtooni and J. Patrick Hornbeck II, eds, (Medieval Church Studies, 23), Turnhout, Brepols, 2012, hardback, pp. xiv, 359, 1 b/w illustration, 2 b/w tables, R.R.P. 90.00, ISBN 9782503534572.

Background: The European Pharmacopoeia specifies Instant Thin-Layer Chromatography Silica Gel (ITLC-SG) as the stationary phase for measuring radiochemical impurities in 99mTc Medronate. The Pall Corporation has stopped manufacturing ITLC-SG. Aim: To investigate chromatography papers as alternatives to ITLC-SG. Experimental: The resolution of the main 99mTc Medronate and impurity peaks were compared on five Whatman papers (1CHR, 31ET, 3MM, 4CHR and 54SFC) using the pharmacopoeial mobile phases: methyl ethyl ketone for detecting 99mTc pertechnetate impurity and sodium acetate solution (136 g/l) for detecting hydrolysed reduced and colloidal 99mTc impurities. The effects of three sample spot treatments (wet, hot dried and air dried) on the distribution of the radiochemical impurities were compared. The levels of radiochemical impurities measured in samples of 99mTc Medronate were compared. Results: The highest resolutions were obtained with 1CHR, 4CHR and 54SFC. Sample spot drying resulted in the measurement of artifactually high levels of 99mTc pertechnetate impurity. When analysing 99mTc Medronate, erroneously high levels of colloidal and 99mTc pertechnetate impurities were measured with 1CHR and 4CHR. Conclusions: 54SFC paper is a suitable alternative to ITLC-SG for measuring radiochemical impurities in 99mTc Medronate. The sample spot should be wet when the paper strip is placed in the chromatography tank. Copyright © 2009 John Wiley & Sons, Ltd.

Objective To determine the circumstances under which sodium chloride injection (SCI) that has been exposed to fluorescent light then used to prepare 99m Tc-MAG3 causes low radiochemical purity (RCP). Methods Two brands of SCI in plastic ampoules (Braun and Steri-Amp) and one in glass vials (Drytec) were exposed to light for up to 7 days then used to prepare 99m Tc-MAG3. RCP was measured by liquid chromatography. To study the effect on the labelling reaction, the reconstituted MAG3 kit was analysed before and after boiling and the formation of the 99m Tc-tartrate intermediate was investigated. Exposed water from plastic ampoules was analysed by mass spectrometry. Results After no exposure, each brand resulted in high RCP 99m Tc-MAG3 (>94%). Drytec SCI produced high RCP throughout (96.7 +/- 0.3%, n=5, 7 days). The RCP produced by Steri-Amp and Braun fell to 85.2 +/- 5.2% and 93.5 +/- 1.6% after exposure for 2 and 4 days, respectively. The chromatogram before boiling contained peaks corresponding to 99m Tc-tartrate and 99m Tc-pertechnetate. After boiling with unexposed SCI, these were minimal and a 99m Tc-MAG3 peak dominated. After boiling with exposed SCI, 99m Tc-pertechnetate and 99m Tc-MAG3 peaks were present. Measurements on tartrate showed a high level of 99m Tc-tartrate before and after boiling with unexposed SCI but a high level of 99m Tc-pertechnetate after boiling with exposed SCI. Mass spectrometry showed that compounds leach into the solution upon exposure to light. Conclusion Preparing 99m Tc-MAG3 using SCI from plastic ampoules that have been exposed to light causes reduced RCP. Exposure of plastic ampoules to light causes leaching of many compounds into the solution. An unknown leached compound destabilizes the 99m Tc-tartrate intermediate complex.