Commercially available C18-solid-phase extraction(SPE) materials, representing packed bed, disc and membrane-types were evaluated for their applicability as effective tools in the sample preparation step of HPLC assays of selective drugs and their metabolites from aqueous and serum samples. Chlorzoxazone (I) and its metabolite 6-hydroxychlorzoxazone (II), phenylbutazone (III) and its metabolite oxyphenylbutazone (IV), and imipramine (V) and its metabolite desipramine (VI) were extracted using each SPE device. In aqueous samples, the highest recoveries of I were achieved with packed bed or C18 disc, whereas the best recoveries of II were achieved with the packed bed-C18. The highest recoveries of III and IV were achieved with packed bed-C18, disc and membrane C18, and the best recoveries of V and VI were achieved with SPEC disc -C18. In serum samples, the highest recoveries of I and II were achieved with packed bed or Empore disc -C18, the best recoveries of III and IV were achieved with packed bed-C18, and SPEC disc C18 and the best recoveries of V and VI were achieved with SPEC disc -C18. The packed-bed and SPEC C18 disc materials were determined to be the best overall devices based on analyte recoveries and precision data.