With the purpose of finding ways to combine micro-bore reversed phase HPLC with ICP-MS detection for analysis of drug substances containing chlorine, bromine and iodine, the suitability of a direct injection nebulizer and an Aridus desolvating microconcentric nebulizer was compared. Using the direct injection nebulizer at flow rates of 25 and 50 µl min−1, the influence of 0–50% methanol and 0–25% acetonitrile on the sensitivity was studied. For chlorine and bromine, the relative sensitivity decreased with increasing amounts of organic solvent. For iodine, the relative sensitivity reached a maximum at low concentrations of organic solvent and then declined with increasing amounts of organic solvent. The response of the direct injection nebulizer was independent of the chemical structure of the analyte. For the desolvating microconcentric nebulizer, the response was dependent on the analyte structure. Many chlorine-, bromine-, and iodine-containing compounds were partially lost in the desolvating unit. For those chlorine- and iodine-containing compounds that were not lost, the sensitivity was independent of methanol concentration in the solvent when a 0–100% methanol gradient was applied.