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 Na2EDTA 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 (Cmax) was 37.69 ng/mL, and the mean time to reach the Cmax (Tmax) was 1.08 h. The area under the plasma concentration-time curve (AUC) and elimination half-life (T1/2) were 106.48 ng/mL/h and 1.66 h, respectively.
Similar content being viewed by others
References
Al Deeb, S. K., Hamdan, I. I., and Al Najjar, S. M., Spectroscopic and HPLC methods for the determination of alendronate in tablets and urine. Talanta, 64, 695–702 (2004).
Hosking, D., Chilvers, C. E., Christiansen, C., Ravn, P., Wasnich, R., Ross, P., McClung, M., Balske, A., Thompson, D., Daley, M., and Yates, A. J., Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group. N. Engl. J. Med., 338, 485–492 (1998).
Hyldstrup, L., Flesch, G., and Hauffe, S. A., Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration. Calcif. Tissue Int., 53, 297–300 (1993).
Kang, H. S., Hwang, S. J., Kim, C. K., and Park, J. S., HPLC method validation and pharmacokinetic study of alendronate sodium in human urine with fluorescence detection. J. Liq. Chromatogr. Relat. Technol., 29, 1589–1600 (2006).
Lin, J. H., Duggan, D. E., Chen, I. W., and Ellsworth, R. L., Physiological disposition of alendronate, a potent antiosteolytic bisphosphonate, in laboratory animals. Drug Metab. Dispos., 19, 926–932 (1991).
Lin, J. H., Chen, I. W., and Duggan, D. E., Effects of dose, sex, and age on the disposition of alendronate, a potent antiosteolytic bisphosphonate, in rats. Drug Metab. Dispos., 20, 473–478 (1992a).
Lin, J. H., Chen, I. W., Deluna, F. A., and Hichens, M., Renal handling of alendronate in rats. An uncharacterized renal transport system. Drug Metab. Dispos., 20, 608–613 (1992b).
Mönkkönen, H., Moilanen, P., Mönkkönen, J., Frith, J. C., Rogers, M. J., and Auriola, S., Analysis of an adenine nucleotide-containing metabolite of clodronate using ion pair high-performance liquid chromatography-electrospray ionisation mass spectrometry. J. Chromatogr. B Biomed. Sci. Appl., 738, 395–403 (2000).
Niemi, R., Taipale, H., Ahlmark, M., Vepsäläinen, J., and Järvinen, T., Simultaneous determination of clodronate and its partial ester derivatives by ion-pair reversed-phase high-performance liquid chromatography coupled with evaporative light-scattering detection. J. Chromatogr. B Biomed. Sci. Appl., 701, 97–102 (1997).
Ptácěk, P., Klíma, J., and Macek, J., Determination of alendronate in human urine as 9-fluorenylmethyl derivative by high-performance liquid chromatography. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 767, 111–116 (2002).
Russell, R. G. and Rogers, M. J., Bisphosphonates: from the laboratory to the clinic and back again. Bone, 25, 97–106 (1999).
Sparidans, R. W. and den Hartigh, J., Chromatographic analysis of bisphosphonates. Pharm. World Sci., 21, 1–10 (1999).
Tarcomnicu, I., Silvestro, L., Savu, S. R., Gherase, A., and Dulea, C., Development and application of a high-performance liquid chromatography-mass spectrometry method to determine alendronate in human urine. J. Chromatogr. A, 1160, 21–33 (2007).
Tsai, E. W., Singh, M. M., Lu, H. H., Ip, D. P., and Brooks, M. A., Application of capillary electrophoresis to pharmaceutical analysis: Determination of alendronate in dosage forms. J. Chromatogr. A, 626, 245–250 (1992).
Usui, T., Watanabe, T., and Higuchi, S., Determination of a new bisphosphonate, YM175, in plasma, urine and bone by high-performance liquid chromatography with electrochemical detection. J. Chromatogr., 584, 213–220 (1992).
Usui, T., Kawakami, R., Watanabe, T., and Higuchi, S., Sensitive determination of a novel bisphosphonate, YM529, in plasma, urine and bone by high-performance liquid chromatography with fluorescence detection. J. Chromatogr., 652, 67–72 (1994).
Wong, J. A., Renton, K. W., Crocker, J. F., O’Regan, P. A., and Acott, P. D., Determination of pamidronate in human whole blood and urine by reversed-phase HPLC with fluorescence detection. Biomed. Chromatogr., 18, 98–101 (2004).
Yakatan, G. J., Poynor, W. J., Talbert, R. L., Floyd, B. F., Slough, C. L., Ampulski, R. S., and Benedict, J. J., Clodronate kinetics and bioavailability. Clin. Pharmacol. Ther., 31, 402–410 (1982).
Yun, M. H. and Kwon, K. I., High-performance liquid chromatography method for determining alendronate sodium in human plasma by detecting fluorescence: application to a pharmacokinetic study in humans. J. Pharm. Biomed. Anal., 40, 168–172 (2006).
Zacharis, C. K. and Tzanavaras, P. D., Determination of bisphosphonate active pharmaceutical ingredients in pharmaceuticals and biological material: a review of analytical methods. J. Pharm. Biomed. Anal., 48, 483–496 (2008).
Zhu, L. S., Lapko, V. N., Lee, J. W., Basir, Y. J., Kafonek, C., Olsen, R., and Briscoe, C., A general approach for the quantitative analysis of bisphosphonates in human serum and urine by high-performance liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom., 20, 3421–3426 (2006).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ban, E., Park, JY., Kim, H.T. et al. 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. Arch. Pharm. Res. 34, 2079–2086 (2011). https://doi.org/10.1007/s12272-011-1211-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-011-1211-z