A better method of quality control for 99mTc-tetrofosmin.

ABSTRACT

UNLABELLED The method of quality control (QC) described on the package insert for (99m)Tc-tetrofosmin requires meticulous attention to technique for accurate radiochemical purity results. About 30 min are needed. Other proposed methods have been validated only with pertechnetate. We developed a convenient new method using silica cartridges. METHODS: A silica cartridge with 7030 methanolwater was determined to be acceptable. The method was validated against sodium pertechnetate ((99m)TcO(4)), (99m)Tc-glucoheptonate, (99m)Tc-sulfur colloid, and low-purity (99m)Tc-tetrofosmin. The validations were made by using a small volume of concentrated (99m)TcO(4) with expired kits. Instant thin-layer chromatography (ITLC) showed 6 impurities after an hour or two. The effects of sample size and flow rate were determined. The precision of repeated tests was determined by comparison with the results of 8 replications on the same batch. The 2 methods were compared at a hospital and at 2 commercial nuclear pharmacies, for a total of 134 replications, with 21 preparations being of <90% radiochemical purity. RESULTS: Volumes between 25 and 100 micro L did not affect the silica-cartridge method but did affect the ITLC method. Flow rate is critical and must be < or =5 mL/min with the silica cartridges. The SD and variance by ITLC were 7 and 51 times larger, respectively. Using the package insert technique as the gold standard, all batches of <90% radiochemical purity were rejected and those of >90% radiochemical purity were accepted. Linear regression gave the following equation ITLC = 1.0051 x silica cartridge (R = 0.99). One- and 2-binned chi(2) analyses gave P values > 0.999999. A 2 x 2 contingency table showed 100% sensitivity, accuracy, and specificity, with a Fisher's exact test P value of 5.7 x 10(-25). Correlation was nearly perfect. CONCLUSION: According to the published rating criteria for alternate radiochemical purity tests (American Pharmacists' Association), the silica-cartridge method has a score of 90.2, versus 65.8 for ITLC. On the basis of published criteria for alternate radiochemical purity testing methods, the new method is clearly seen to be superior. Furthermore, alternate methods were validated only with free (99m)TcO(4) and colloidal impurities. We showed that these are not the significant radiochemical impurities with (99m)Tc-tetrofosmin and that those methods are not valid. This new method is fast, convenient, accurate, safe, and economical, but careful control of flow rate is required.