Radio-LC-MS for the characterization of Tc-99m-labeled bioconjugates

This report describes the first example of using radio-LC-MS for determinin g the composition of Tc-99m radiopharmaceuticals at the tracer level. The i n-line radiometric detector is a useful addition to a standard LC-MS and pr ovides direct correlation between the MS data and the radioactive species i n a radiopharmaceutical kit. Complexes [Tc-99m(HYNICtide)(tricine)(L)] (RP4 44, L = TPPTS; RP445, L = TPPDS; and RP446, L = TPPMS) were prepared using a decayed generator eluant. All the ternary ligand Tc-99m complexes show th e expected monoprotonated molecular ions, (M + 1)(+), and diprotonated mole cular ions, (M + 2)(2+). The LC-MS spectral data support the proposed struc ture and are consistent with those obtained for their corresponding Tc-99 a nalogues. Ternary ligand complexes [Tc-99m(HYNICtide)(tricine)(L)] (L = ISO NIC-HE and ISONIC-Sorb) are neutral, and the molecular weights are also low er than that of RP444. Using a fresh generator eluant (24 h prior elution), only 1-2 mCi of Tc-99m [(7 x 10(-12))-(1.5 x 10(-11)) mol of technetium co mplex] are required to obtain a reasonably clean mass spectrum. Radio-LC-MS is a quick and accurate analytical tool for characterization of Tc-99m rad iopharmaceuticals at the tracer level.