We propose a version of the simultaneous determination of zoledronic acid and creatinine in serum and plasma samples by hydrophilic chromatography (HILIC). Factors affecting the determination of zoledronic acid were found: the composition and concentration of the buffer solution, the nature of the stationary phase, the presence of tartaric acid in the eluent as a complexing agent to prevent the complexation of zoledronic acid with metal ions. We determined the linear concentration ranges for zoledronic acid and creatinine and their limits of detection. The following conditions for chromatographic analysis were found: amide stationary phase; a 5 mM phosphate buffer solution, 2 mM tartaric acid (pH 7.0)/CH3CN; gradient 90-70% of CH3CN.