Optimization of an HPLC-PDA analytical method for therapeutic monitoring of oral busulfan in hematopoietic stem cell transplant patients

Authors

DOI:

https://doi.org/10.33448/rsd-v10i6.15864

Keywords:

Busulfan; HPLC; Therapeutic drug monitoring.

Abstract

The study aims to develop activities for therapeutic monitoring of oral busulfan in patients undergoing heterologous stem-cell transplantation (HSCT) through the identification and determination of plasma busulfan. It was used HPLC-PDA Shimadzu C18 column (150 mm x 4 mm), methanol/water/acetonitrile (65:20:15, v/v/v), flow rate 1 mL min-1, UV λ=276 nm, analysis time 17 min; derivatization with sodium diethylcarbamate, extraction with ethyl acetate; linear calibration curve over the range of 200-5000 ng ml-1. The average relative recovery of the controls was 89% ± 0.04 (QCH=86%; QCM=87%; QCL=93%), and the internal standard (IS) was 74%±0.47. The mean absolute recovery of the controls was 114±0.03% (QCH=111%, QCM=118%; QCL=113%), and the IS was 102±2.5%. The lower limits of detection and quantification obtained were respectively 200 ng ml-1 and 40 ng.mL-1. The linearity was evaluated by calibration curve (200-5000 ng.mL-1) (r=0.998, r=0.994, r=0.998). The repeatability (intracorrida) resulted in 1.25% -11.25% and intermediate precision (intercorrida) resulted in 2.17% -10.71%. The accuracy was found to be 89.61% -102.18%. The short-term stability of the solutions and samples extracted was 6.25% and 3.18% for QCL, 7.54% and 2.4% for QCH, and 4.13% and 13.17% for IS, respectively. The stability of freeze-thaw cycles extracted samples and the solutions was 3.64% and 2.53% for QCL, 9.09% and 5.65% and QCH to 4.82% and 10.32% for IS, respectively. It was concludefd that it was possible to describe a technique for determining the busulfan in plasma by HPLC-PDA, settling their validation parameters for therapeutic drug monitoring purposes.

References

Balasubramanian, P., Srivastava, A., Chandy, M. (2001). Stability of busulfan in frozen plasma and whole blood samples. Clinical Chemistry, 47(4):766-8.

Bleyzac, N, Barou P, Aulagner G. (2000). Rapid and sensitive high performance liquid chromatographic method for busulfan assay in plasma. Journal of Chromatography B Biomedical Sciences and Applications, 742(2):427-32.

Bornhäuser, M. et al. (2003). Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells. Blood., 102(3):820-6.

Brasil. Ministério da Saúde. (2003). Agência Nacional de Vigilância Sanitária. Resolução – RE nº 899, de 29 de maio de 2003. Diário Oficial da União, Brasília (DF).

Bullock, J. M., Smith, P. F., Booker, B. M., Loughner, J., Capozzi, D., Mccarthy, Junior, P. L., Shaw, L. M. (2006). Development of a pharmacokinetic and Bayesian optimal sampling model for individualization of oral busulfan in hematopoietic stem cell transplantation. Therapeutic Drug Monitoring, 28(1):62-6.

Chow, D. S. L., Bhagwatwar, H. P., Phadungpojna, S., Andersson, B. S. (1997). Stability-indicating high-performance liquid chromatographic assay of busulfan in aqueous and plasma samples. Journal of Chromatography B Biomedical Sciences and Applications., 704(1–2):277–88.

Ciurea, S. O., Andersson, B. S. (2009). Busulfan in hematopoietic stem cell transplantation. Biologic Blood Marrow Transplantation, 15(5):523–36.

Corbacioglu, S., Jabbour, E. J., Mohty, M. (2019) Risk Factors for Development of and Progression of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome. Biological Blood Marrow Transplantation. 2019 Jul;25(7):1271-1280.

Effting, C., Arantes, A. M., Labre, L.V. Q., Carneiro, W. J., Oliveira-Neto, J. R., Bariani, C., Rodrigues, C. R., Rodrigues, A. R., Cunha, L. C. (2015). Individualizing oral busulfan dose after using a test dose in patients undergoing hematopoietic stem cell transplantation: pharmacokinetic characterization. Therapeutic Drug Monitoring, 37 (1), 66-70.

Feng, X., Wu, Y., Zhang, J., Li, J., Zhu, G., Fan, D., Yang, C., Zhao, L. (2020) Busulfan systemic exposure and its relationship with efficacy and safety in hematopoietic stem cell transplantation in children: a meta-analysis. BMC Pediatrics. Apr 20;20(1):176.

Hara, S., Tsuchie, M., Tsujioka, R., Kimura. M., Fuji, M., Kuroda, T., Ono, N. (2000). High-performance liquid chromatographic quantification of busulfan in human serum after fluorescence derivatization by 2-naphthalenethiol. Analytical Sciences, 16(3):287-91.

Hassan, M. et al. (2000). The effect of busulphan on the pharmacokinetics of cyclophosphamide and its 4-hydroxy metabolite: time interval influence on therapeutic efficacy and therapy-related toxicity. Bone Marrow Transplantation, 25(9):915-24.

Heggie, J. R., Wu, M., Burns, R. B., Ng, C. S., Fung, H. C., Knight, G., Barnett, M. J., Spinelli, J. J., Embree, L. (1997). Validation of a high-performance liquid chromatographic assay method for pharmacokinetic evaluation of busulfan. Journal of Chromatography B Biomedical Sciences and Applications, 692(2):437-44.

ICH Harmonised Tripartite Guideline. (2005). International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland.

Lawson, R., Staatz, C. E., Fraser, C. J., Hennig, S. (2021) Review of the Pharmacokinetics and Pharmacodynamics of Intravenous Busulfan in Paediatric Patients. Clinical Pharmacokinetics. Jan; 60(1):17-51.

Nath, C. E., Shaw, P. J. (2007). Busulfan in blood and marrow transplantation: dose, route, frequency, and role of therapeutic drug monitoring. Current Clinical Pharmacology, 2(1):75-91.

Peris JE, Latorre JA, Castel V, Verdeguer A, Esteve S, Torres-Molina F. (1999). Determination of busulfan in human plasma using high-performance liquid chromatography with pre-column derivatization and flurescence detection. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 730(1):33-40.

Philippe, M., Neely, M., Rushing, T., Bertrand, Y., Bleyzac, N., Goutelle, S. (2019) Maximal concentration of intravenous busulfan as a determinant of veno-occlusive disease: a pharmacokinetic-pharmacodynamic analysis in 293 hematopoietic stem cell transplanted children. Bone Marrow Transplantation. Mar;54(3):448-457.

Quernin, M. H., Poonkuzhali, B., Médard, Y., Dennison, D., Srivastava, A., Krishnamoorthy, R., Chandy, M., Jacqz-Aigrain, E. (1999). High-performance liquid chromatographic method for quantification of busulfan in plasma after derivatization by tetrafluorotiophenol. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 721(1):147-52.

Salman, B., Al-Khabori, M., Al-Huneini, M., Al-Rawas, A., Dennison, D., Al-Za'abi, M. (2020) Busulfan clearance does not predict the development of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation. International Journal of Hematology, Aug;112(2):210-216.

Slattery, J. T. et al. (1997). Marrow transplantation for chronic myeloid leukemia: the influence of plasma busulfan levels on the outcome of transplantation. Blood., 89(8):3055-60.

Slattery, J. T., Risler, L. J. (1998). Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation. Therapeutic Drug Monitoring, 20(5):543-49.

Tabak, A., Hoffer, E., Rowe, J. M., Krivoy, N. (2001). Monitoring of busulfan area under the curve: estimation by a single measurement. Therapeutic Drug Monitoring, 23(5):526-8.

Takamatsu, Y., Ogata, K., Yamauchi, K., Hara, S., Kamimura, T., Hayashi, S., Suzumiya, J., Tamura, K. (2005). An evaluation of busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation. Japanese Journal of Clinical Oncology, 35(7):400-3.

Tran, H. T., Madden, T., Petropoulos, D., Worth, L. L., Felix, E. A., Sprigg-Saenz, H. A., Choroszy, M., Danielson, M., Przepiorka, D., Chan, K. W. (2000). Individualizing high-dose oral busulfan: prospective dose adjustment in a pediatric population undergoing allogeneic stem cell transplantation for advanced hematologic malignancies. Bone Marrow Transplantation, 26(5):463-70.

Published

07/06/2021

How to Cite

EFFTING, C. .; OLIVEIRA, F. G. F. .; MUNDIM, I. M. .; CRUZ, A. de C.; RODRIGUES, A. R. .; RODRIGUES, C. R. .; OLIVEIRA-NETO, J. R. de .; CUNHA, M. M. B. da .; ARANTES, A. de M. .; CUNHA, L. C. da. Optimization of an HPLC-PDA analytical method for therapeutic monitoring of oral busulfan in hematopoietic stem cell transplant patients. Research, Society and Development, [S. l.], v. 10, n. 6, p. e48110615864, 2021. DOI: 10.33448/rsd-v10i6.15864. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/15864. Acesso em: 23 jun. 2021.

Issue

Section

Health Sciences