Determination of the radiochemical purity of (99m) Tc medronate injection by thin layer chromatography on iTLC-SG: effect of medronate concentration on the value measured.

BACKGROUND: 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. AIM: The goal of this study was to determine if the concentration of medronate influences the value obtained for (99m) Tc pertechnetate impurity. EXPERIMENTAL: (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. 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 (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. CONCLUSIONS: 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.

Effect of 99Tc on the radiochemical purity of 99mTc radiopharmaceuticals.

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<0.05) were found between the RCPs of control and test samples of albumin nanocolloid, mertiatide and sestamibi 1 h after preparation. In each, the test sample had lower RCP, but was satisfactory. Similar results were found for macrosalb with added Tc, but the RCPs of the test samples were unsatisfactory at 83.9±4.2%. The RCPs of all control and test samples were satisfactory at expiry. CONCLUSION: Seven of the eight radiopharmaceuticals tested can safely be prepared using eluate from a generator that has remained uneluted for 7 days. Under these conditions, care must be taken when preparing Tc-macrosalb, as its RCP remains unsatisfactory up to 2 h after preparation.

Preparation of 99mTc radiopharmaceuticals: the effect on radiochemical purity of using sodium chloride injection from plastic ampoules that have been exposed to light.

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.

Preparation of 99m Tc-MAG3: the effect on radiochemical purity of using sodium chloride injection from plastic ampoules that have been exposed to light.

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.

Preparation of 99mTc-Nanocoll for use in sentinel node localization: Validation of a protocol for supplying in unit-dose syringes.

OBJECTIVES: To determine if 99mTc-Nanocoll is affected by storage in a syringe, passage through an R-Lock or mixing with Patent Blue V dye. METHODS: 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 particles >100 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. RESULTS: In all samples, adsorption of 99mTc on syringes was <1%, 99mTc-pertechnetate impurity was <2%, >95% of 99mTc was labelled to particles <100 nm in diameter, the mean particle diameter was 6.6 nm and the particles had a diameter of <12 nm. All tests showed no significant difference (P > 0.05, 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. CONCLUSIONS: 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.

Preparation of 99mTc-MAG3: radiochemical purity is affected by the residence time of sodium chloride injection in a three-part syringe.

BACKGROUND: 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. OBJECTIVES: To investigate the cause of this phenomenon, determine how it can be avoided and establish whether it occurs with other 99mTc radiopharmaceuticals. METHODS: 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. RESULTS: 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 (P<0.05, 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 (P>0.05, 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 (P>0.05, n=5). CONCLUSIONS: 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.

A comparison of techniques for analysing 90Y-Zevalin thin-layer chromatography plates.

OBJECTIVES: To simulate 90Y-Zevalin thin-layer chromatograms representing a range of radiochemical purities, to compare the radiochemical purities obtained with five techniques used to quantify 90Y on the plates and to measure 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 < or =0.3%. The signal to background ratios were satisfactory, ranging from 24 to 2.1 x 10(5). CONCLUSION: Each technique is suitable for analysing 90Y-Zevalin TLC plates.