A novel HPLC-UV method for determining alendronate in rat plasma through precolumn derivatization with phenyl isothiocyanate: Application to pharmacokinetics

摘要

The determination of alendronate (ALE) in biofluids using a low-cost instrument is potentially useful in preclinical pharmacokinetic studies. This study developed and validated a high-performance liquid chromatography with ultraviolet method for ALE determination in rat plasma using precolumn derivatization with phenyl isothiocyanate (PITC). Inhibiting compounds in the samples were first eliminated using solid-phase extraction. ALE in the sample was subsequently allowed to react with PITC to form a phenylthiocarbamoyl derivative for further analysis. The assay was linear within the concentration range of 0.29-25.0 mu g/mL. The precision and accuracy were less than 3.9% and 98.0 +/- 3.9%, respectively. The limits of detection and quantification were 0.08 and 0.20 mu g/mL, respectively. The method was successfully used to evaluate the pharmacokinetic parameters of ALE in rats following a single oral administration (30.0 mg/kg). The results show that the peak plasma ALE concentration is 0.69 +/- 0.18 mu g/mL. The area under the plasma concentration-time curve value of ALE was 2.14 +/- 0.68 mu g/mL hr. This method can suitably evaluate the bioavailabilities of different ALE dosage forms in preclinical pharmacokinetic studies.