一种用于99mTc-替曲膦的更好的质量控制方法。

Hammes Richard, Joas Lori A, Kirschling Thomas E, Ledford Jamie R, Knox Tara L, Nybo Mark R, Sterzinger John J

Nuclear Medicine E1/382C, University of Wisconsin Hospital and Clinics, Madison, WI 53706, USA.

J Nucl Med Technol. 2004 Jun;32(2):72-8.

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 70:30 methanol:water 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.

未标注

（99m）锝替曲膦包装说明书中描述的质量控制（QC）方法需要严格注意技术细节才能获得准确的放射化学纯度结果。大约需要30分钟。其他提出的方法仅用高锝酸盐进行了验证。我们开发了一种使用硅胶柱的便捷新方法。

方法

确定含70:30甲醇:水的硅胶柱是可接受的。该方法针对高锝酸钠（（99m）TcO₄）、（99m）锝葡庚糖酸盐、（99m）锝硫胶体和低纯度（99m）锝替曲膦进行了验证。验证使用少量浓缩的（99m）TcO₄和过期试剂盒。即时薄层色谱法（ITLC）在一两个小时后显示出6种杂质。确定了样品量和流速的影响。通过与同一批次8次重复结果比较确定重复测试的精密度。在一家医院和两家商业核药房比较了这两种方法，共进行了134次重复，其中21份制剂的放射化学纯度<90%。

结果

25至100微升之间的体积不影响硅胶柱法，但影响ITLC法。流速至关重要，使用硅胶柱时必须≤5毫升/分钟。ITLC法的标准差和方差分别大7倍和51倍。以包装说明书方法作为金标准，所有放射化学纯度<90%的批次均被拒收，而纯度>90%的批次被接受。线性回归得出以下方程：ITLC = 1.0051×硅胶柱（R = 0.99）。单箱和双箱卡方分析得出P值>0.999999。2×2列联表显示敏感性、准确性和特异性均为100%，费舍尔精确检验P值为5.7×10⁻²⁵。相关性几乎完美。

结论

根据已发表的替代放射化学纯度测试评级标准（美国药剂师协会），硅胶柱法得分为90.2，而ITLC法为65.8。根据已发表的替代放射化学纯度测试方法标准，新方法明显更优。此外，替代方法仅用游离（99m）TcO₄和胶体杂质进行了验证。我们表明这些不是（99m）锝替曲膦的主要放射化学杂质，那些方法无效。这种新方法快速、便捷、准确、安全且经济，但需要仔细控制流速。