Determination of alendronate in low volumes of plasma by column-switching high-performance liquid chromatography method and its application to pharmacokinetic studies in human plasma

Abstract

A sensitive and simple column-switching high-performance liquid chromatographic (HPLC) method with fluorescence detection was developed for the determination of alendronate in human plasma. Alendronate and pamidronate (internal standard, IS) in plasma including Na(2)EDTA were precipitated with sodium hydroxide and calcium chloride after deproteinization using 10% trichloroacetic acid solution. The precipitated alendronate and IS were reconstituted by sodium citrate and citric acid and then derivatized with 9-fluorenylmethyl chloroformate. The resulting solution was injected onto an HPLC system consisting of a pretreatment column and an analytical column, which were connected with a six-port switching valve. The assay was linear in the concentration range of 2-100 ng/mL in 1 mL of plasma with high precision and accuracy, and the limit of detection was 0.5 ng/mL. It was successfully applied to evaluate the pharmacokinetic parameters of alendronate in human volunteers following single oral administration. The mean value of maximum alendronate plasma concentration (C(max)) was 37.69 ng/mL, and the mean time to reach the C(max) (T(max)) was 1.08 h. The area under the plasma concentration-time curve (AUC) and elimination half-life (T(1/2)) were 106.48 ng/mL/h and 1.66 h, respectively.

A fast and simple spectrofluorometric method for the determination of alendronate sodium in pharmaceuticals

“…However, our method has some advantages as well as high sensitivity, simplicity and low cost compared to the other techniques such as HPLC and electrochemical technique and can be easily used for the alendronate determination. 2 , 3 , 5 , 9 , 10 …”

“… 1 , 2 , 4 Besides, the use of chemical derivatisation of alendronate with OPA not only improves the separation of the analyte but also after some optimization, it enhances the detection sensitivity. 2 , 5 Therefore, spectrofluorimetric method for quantifying alendronate sodium in pure and tablet has been developed and validated for the first time. The technique has advantages such as simplicity and low cost.…”

Symposium: Imaging modalities for drug-related osteonecrosis of the jaw (6), assessment of mandibular metabolism due to long-term administration of an anti-resorptive agent by bone scintigraphy (secondary publication)

“…The elimination half-life (T1/2) of the BP alendronate is 1.66 h, and the T1/2 of the BP zoledronate is multiphasic, with 0.2 and 1.4 h representing early and late phases, respectively [14], [15]. BP binds to bone rapidly by chelating calcium ions on hydroxyapatite surfaces [16].…”

A simple innovative spectrofluorometric method for the determination of alendronate in bulk and in pharmaceutical tablets

“…Non‐fluorescent compounds can also be measured indirectly or after chemical derivatization using a fluorogenic or a fluorophoric agent. Bisphosphonates have been determined by spectrofluorometry using fluorescamine, 9‐fluorenylmethyl chloroformate, o ‐phthalaldehyde, and phenyl isothiocyanate . These methods suffer from long reaction times, high costs of derivatizing agents and complicated procedures.…”