TY - JOUR
T1 - Quantification of urinary derivatives of Phenylbutyric and Benzoic acids by LC-MS/MS as treatment compliance biomarkers in Urea Cycle disorders
AU - Andrade, Fernando
AU - Vitoria, Isidro
AU - Martín Hernández, Elena
AU - Pintos-Morell, Guillem
AU - Correcher, Patricia
AU - Puig-Piña, Rocío
AU - Quijada-Fraile, Pilar
AU - Peña-Quintana, Luis
AU - Marquez, Ana Mª
AU - Villate, Olatz
AU - García Silva, Mª Teresa
AU - de las Heras, Javier
AU - Ceberio, Leticia
AU - Rodrigues, Esmeralda
AU - Almeida Campos, Teresa
AU - Yahyaoui, Raquel
AU - Blasco, Javier
AU - Vives-Piñera, Inmaculada
AU - Gil, David
AU - del Toro, Mireia
AU - Ruiz-Pons, Mónica
AU - Cañedo, Elvira
AU - Barba Romero, Miguel Angel
AU - García-Jiménez, Mª Concepción
AU - Aldámiz-Echevarría, Luis
PY - 2019/11/30
Y1 - 2019/11/30
N2 - © 2019 Elsevier B.V. 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.
AB - © 2019 Elsevier B.V. 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.
KW - Benzoic acid
KW - Hyperammonaemia
KW - Phenylbutyric acid
KW - Stability
KW - Tandem mass spectrometry
KW - Urea cycle disorders
U2 - 10.1016/j.jpba.2019.112798
DO - 10.1016/j.jpba.2019.112798
M3 - Article
C2 - 31394303
VL - 176
M1 - 112798
ER -