II-VI semiconductor heterostructures have been studied using time-of-flight secondary ion mass spectrometry (TOF-SIMS) depth profiling. We demonstrate the use of binary negative cluster ions, such as CdSe- and CdSe2-, to simultaneously monitor the CI doping and Cd growth profiles of n-type modulation-doped ZnSe:Cl/ZnxCd1-xSe multiple quantum well (MQW) structures in negative ion TOF-SIMS depth profiling. Zn and Cd profiles of MQW structure ZnTe/CdSe are monitored by ZnTe2- and CdSe2- with Te- and Se- simultaneously in negative ion TOF-SIMS depth profiling, so as to avoid the mass interference of ZnTe- and CdSe-. Sputtering rates of numerous II-VI semiconductor epilayers and depth resolution of interface abruptness have been determined. The substitution of either element in ZnSe epilayer by Cd or Te gives a lower sputtering rate. This trend is illustrated by the decrease of sputtering rate on the order of ZnSe, ZnTe, to CdSe, where ZnTe and CdSe have relatively the same sputtering rate. Depth profiling of n-type modulation-doped ZnSe:Cl/ZnxCd1-xSe MQW structure yields a broadening effect due to cascade mixing, which is strongly sputtered-depth dependent. However, the knock-on effect is unrelated to the sputtered depth.