Tags

Type your tag names separated by a space and hit enter

Simultaneous quantification of succinylacetone and nitisinone for therapeutic drug monitoring in the treatment of Tyrosinemia type 1.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 01; 1072:259-266.JC

Abstract

We present a straightforward and robust method for simultaneous quantification of succinylacetone and nitisinone in plasma using LC-ESI-MS/MS. The method has been developed for routine therapeutic drug monitoring in hepatorenal tyrosinemia type 1 (HT1) patients undergoing nitisinone treatment. Previous methods are based on separate analyses of succinylacetone and nitisinone, often using the potentially harmful compound hydrazine for derivatization of the former. In the present procedure, succinylacetone is derivatized in a single-step using butanolic HCl. Analyte extraction and sample clean-up is carried out by simple protein precipitation. The linear range for both analytes is 0.1 up to 125μM, covering the vast majority of encountered levels in real-life samples. The sensitivity and limit of quantification allows measurement of succinylacetone in the therapeutical range for HT1 patients. Stability studies show that succinylacetone is highly sensitive to storage conditions, whereas nitisinone shows little to no degradation. Correct sample handling is therefore important for reliable results when monitoring succinylacetone concentrations.

Authors+Show Affiliations

Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29195145

Citation

Sundberg, Jonas, et al. "Simultaneous Quantification of Succinylacetone and Nitisinone for Therapeutic Drug Monitoring in the Treatment of Tyrosinemia Type 1." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 1072, 2018, pp. 259-266.
Sundberg J, Wibrand F, Lund AM, et al. Simultaneous quantification of succinylacetone and nitisinone for therapeutic drug monitoring in the treatment of Tyrosinemia type 1. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1072:259-266.
Sundberg, J., Wibrand, F., Lund, A. M., & Christensen, M. (2018). Simultaneous quantification of succinylacetone and nitisinone for therapeutic drug monitoring in the treatment of Tyrosinemia type 1. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 1072, 259-266. https://doi.org/10.1016/j.jchromb.2017.11.031
Sundberg J, et al. Simultaneous Quantification of Succinylacetone and Nitisinone for Therapeutic Drug Monitoring in the Treatment of Tyrosinemia Type 1. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 1;1072:259-266. PubMed PMID: 29195145.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simultaneous quantification of succinylacetone and nitisinone for therapeutic drug monitoring in the treatment of Tyrosinemia type 1. AU - Sundberg,Jonas, AU - Wibrand,Flemming, AU - Lund,Allan Meldgaard, AU - Christensen,Mette, Y1 - 2017/11/26/ PY - 2017/07/31/received PY - 2017/11/22/revised PY - 2017/11/24/accepted PY - 2017/12/2/pubmed PY - 2018/2/22/medline PY - 2017/12/2/entrez KW - Bioanalysis KW - Liquid chromatography KW - Mass spectrometry KW - Nitisinone KW - Parallelism KW - Succinylacetone KW - Tyrosinemia SP - 259 EP - 266 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. VL - 1072 N2 - We present a straightforward and robust method for simultaneous quantification of succinylacetone and nitisinone in plasma using LC-ESI-MS/MS. The method has been developed for routine therapeutic drug monitoring in hepatorenal tyrosinemia type 1 (HT1) patients undergoing nitisinone treatment. Previous methods are based on separate analyses of succinylacetone and nitisinone, often using the potentially harmful compound hydrazine for derivatization of the former. In the present procedure, succinylacetone is derivatized in a single-step using butanolic HCl. Analyte extraction and sample clean-up is carried out by simple protein precipitation. The linear range for both analytes is 0.1 up to 125μM, covering the vast majority of encountered levels in real-life samples. The sensitivity and limit of quantification allows measurement of succinylacetone in the therapeutical range for HT1 patients. Stability studies show that succinylacetone is highly sensitive to storage conditions, whereas nitisinone shows little to no degradation. Correct sample handling is therefore important for reliable results when monitoring succinylacetone concentrations. SN - 1873-376X UR - https://www.unboundmedicine.com/medline/citation/29195145/Simultaneous_quantification_of_succinylacetone_and_nitisinone_for_therapeutic_drug_monitoring_in_the_treatment_of_Tyrosinemia_type_1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1570-0232(17)31325-9 DB - PRIME DP - Unbound Medicine ER -