Four different methods for determining the radiochemical purity (RCP) of 99Tcm-sestamibi have been proposed to replace the recommended thin-layer chromatography (TLC) method, as the recommended method is inconvenient and time-consuming. The purpose of this study was to compare the recommended TLC method with the four proposed rapid QC methods for 99Tcm-sestamibi: (1) chloroform extraction (CE), (2) mini-paper chromatography with chloroform/tetrahydrofuran (1:1, v/v) (MPC), (3) Waters Sep-Pak alumina N cartridge with 100% ethanol (SPE), and (4) Waters Sep-Pak C18 cartridge with normal saline (SPNS). For RCP values ranging from 21.8 to 98.7% (n = 20), both the CE and SPNS methods produced falsely high RCP values (RCP difference: 14.1 +/- 23.5% for CE and 15.0 +/- 24.9% for SPNS). The MPC and SPE methods were in good agreement (r = 0.98 for MPC and 0.88 for SPE) with the recommended TLC method over the critical RCP range (i.e. 77.0-98.7%, n = 52) (RCP difference: -0.9 +/- 1.2% for MPC and -4.3 +/- 3.2% for SPE). None of the 99Tcm-sestamibi preparations that had been rejected (i.e. RCP < 90%) by the TLC method were accepted by either the MPC or SPE method. However, 4 of the 52 99Tcm-sestamibi preparations with acceptable RCP by the TLC method had unacceptable RCP by the MPC method, whereas 8 of the same 52 preparations were unacceptable by the SPE method.(ABSTRACT TRUNCATED AT 250 WORDS)