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
; 1072: 259-266, 2018 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-29195145
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Monitoring
/
Tyrosinemias
/
Cyclohexanones
/
Heptanoates
/
Nitrobenzoates
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
J Chromatogr B Analyt Technol Biomed Life Sci
Journal subject:
ENGENHARIA BIOMEDICA
Year:
2018
Document type:
Article
Affiliation country:
Denmark