학술논문
Quantification of urinary derivatives of Phenylbutyric and Benzoic acids by LC-MS/MS as treatment compliance biomarkers in Urea Cycle disorders.
Document Type
Academic Journal
Author
Andrade F; Group of Metabolism, Biocruces Bizkaia Health Research Institute, linked clinical group of Rare Diseases CIBER (CIBERER), Barakaldo, Spain.; Vitoria I; Unit of Metabolopathies, La Fe University Hospital, Valencia, Spain.; Martín Hernández E; Pediatric Rare Diseases Unit, Metabolic and Mitochondrial Diseases, Pediatric Department, 12 de Octubre University Hospital, Research Institute (i+12), Madrid, Spain.; Pintos-Morell G; Centre for Rare Diseases, University Hospital Vall d´Hebron, Barcelona. Research Institute Germans Trias I Pujol (IGTP), CIBERER-GCV08, Universitat Autònoma de Barcelona, Badalona, Spain.; Correcher P; Unit of Metabolopathies, La Fe University Hospital, Valencia, Spain.; Puig-Piña R; Department of Endocrinology and Nutrition. Adult Metabolic Unit. University Hospital Germans Trias i Pujol, Badalona, Spain.; Quijada-Fraile P; Pediatric Rare Diseases Unit, Metabolic and Mitochondrial Diseases, Pediatric Department, 12 de Octubre University Hospital, Research Institute (i+12), Madrid, Spain.; Peña-Quintana L; Pediatric Gastroenterology, Hepatology and Nutrition Unit, Mother-Child University Hospital of Canarias, Ciber OBN, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.; Marquez AM; Pediatric Gastroenterology and Nutrition Unit, Mother-Child Hospital of Badajoz, Spain.; Villate O; Group of Metabolism, Biocruces Bizkaia Health Research Institute, linked clinical group of Rare Diseases CIBER (CIBERER), Barakaldo, Spain.; García Silva MT; Pediatric Rare Diseases Unit, Metabolic and Mitochondrial Diseases, Pediatric Department, 12 de Octubre University Hospital, Research Institute (i+12), Madrid, Spain.; de Las Heras J; Group of Metabolism, Biocruces Bizkaia Health Research Institute, linked clinical group of Rare Diseases CIBER (CIBERER), Barakaldo, Spain.; Ceberio L; Group of Metabolism, Biocruces Bizkaia Health Research Institute, linked clinical group of Rare Diseases CIBER (CIBERER), Barakaldo, Spain.; Rodrigues E; Department of Pediatrics, Centro Hospitalar de Sao Joáo, Porto, Portugal.; Almeida Campos T; Department of Pediatrics, Centro Hospitalar de Sao Joáo, Porto, Portugal.; Yahyaoui R; Inherited Metabolic Disease Laboratory, Institute of Biomedical Research in Málaga (IBIMA), Málaga Regional University Hospital, Málaga, Spain.; Blasco J; Gastroenterology, Hepatology and Child Nutrition Unit, Carlos Haya University Hospital, Málaga, Spain.; Vives-Piñera I; Gastroenterology Unit, Virgen de la Arrixaca University Hospital, Murcia, Spain.; Gil D; Gastroenterology Unit, Virgen de la Arrixaca University Hospital, Murcia, Spain.; Del Toro M; Pediatric Neurology Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain.; Ruiz-Pons M; Pediatric Nutrition Unit, Nuestra Señora de la Candelaria University Hospital, Santa Cruz de Tenerife, Spain.; Cañedo E; Gastroenterology and Nutrition Unit, Niño Jesús University Hospital, Madrid, Spain.; Barba Romero MA; Department of Internal Medicine, Albacete University Hospital, Castilla-La Mancha University, Spain.; García-Jiménez MC; Metabolic diseases Unit, Miguel Servet University Hospital, Zaragoza, Spain.; Aldámiz-Echevarría L; Group of Metabolism, Biocruces Bizkaia Health Research Institute, linked clinical group of Rare Diseases CIBER (CIBERER), Barakaldo, Spain. Electronic address: luisjose.aldamiz-echevarazuara@osakidetza.eus.
Source
Publisher: Elsevier Science Country of Publication: England NLM ID: 8309336 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-264X (Electronic) Linking ISSN: 07317085 NLM ISO Abbreviation: J Pharm Biomed Anal Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: Salts of phenylacetic acid (PAA) and phenylbutyric acid (PBA) have been used for nitrogen elimination as a treatment for hyperammonaemia caused by urea cycle disorders (UCD). A new analytical method for PBA measurement in urine which helps to evaluate the drug adherence has been implemented.
Methods: Urine specimens from UCD patients receiving PBA were analysed by tandem mass spectrometry to measure urine phenylacetylglutamine (PAGln). Some clinical and biochemical data for each patient were collected.
Results: Our study included 87 samples from 40 UCD patients. The PAGln levels did not correlate with height, weight or age. However, the PAGln values showed correlation with PBA dose (r = 0.383, P = 0.015). Plasma glutamine and ammonia levels presented a positive correlation (r = 0.537, P < 0.001). The stability for PAGln in urine was determined at different storage temperatures.
Conclusions: We have developed a simple method for the determination of PAGln in urine, which acts as useful biomarker of effective drug delivery. PAGln in urine is stable at room temperature at least for 15 days, and for several months when frozen at -20 °C. This procedure is useful for the optimization and monitorization of the drug dose allowing the use of spot urine samples.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Methods: Urine specimens from UCD patients receiving PBA were analysed by tandem mass spectrometry to measure urine phenylacetylglutamine (PAGln). Some clinical and biochemical data for each patient were collected.
Results: Our study included 87 samples from 40 UCD patients. The PAGln levels did not correlate with height, weight or age. However, the PAGln values showed correlation with PBA dose (r = 0.383, P = 0.015). Plasma glutamine and ammonia levels presented a positive correlation (r = 0.537, P < 0.001). The stability for PAGln in urine was determined at different storage temperatures.
Conclusions: We have developed a simple method for the determination of PAGln in urine, which acts as useful biomarker of effective drug delivery. PAGln in urine is stable at room temperature at least for 15 days, and for several months when frozen at -20 °C. This procedure is useful for the optimization and monitorization of the drug dose allowing the use of spot urine samples.
(Copyright © 2019 Elsevier B.V. All rights reserved.)