TY - JOUR
T1 - Serum levels of risperidone and its metabolite, 9-hydroxyrisperidone
T2 - Correlation between drug concentration and clinical response
AU - Lostia, Alfonso M.
AU - Mazzarini, Lorenzo
AU - Pacchiarotti, Isabella
AU - Lionetto, Luana
AU - Rossi, Pietro De
AU - Sanna, Livia
AU - Sani, Gabriele
AU - Kotzalidis, Giorgio D.
AU - Girardi, Paolo
AU - Simmaco, Maurizio
AU - Tatarelli, Roberto
PY - 2009/8
Y1 - 2009/8
N2 - The aim of this study was to assess a method able to analyze serum levels of risperidone (RIS) and its metabolite, 9-hydroxyrisperidone (9-OH-RIS), and to investigate possible relationships between changes in serum concentrations of these drugs and clinical measures, so to identify early markers of treatment response. The authors developed a sensitive and specific liquid chromatography-tandem mass spectrometry method to measure RIS and its metabolite in serum. Fifteen RIS-naive patients were admitted to an acute psychiatric care unit and treated with 4-6 mg/d oral RIS. At days 7 and 21 of hospital stay, serum levels were measured; clinical scales and serum prolactin were assessed. RIS and its metabolite were analyzed by a Q-Trap 2000 triple quadrupole/ion trap mass spectrometer in the multiple reaction-monitoring mode. Chromatographic separation was accomplished using a cyano column with an analytical run of 9 minutes. The calibration curve exhibited consistent linearity and reproducibility in the range 0-100 ng/mL for both analytes. Lower limit of quantification was 0.2 ng/mL; limit of detection, for a signal to noise ratio of 3, was 0.05 ng/mL for both analytes. Serum RIS and 9-OH-RIS levels increased at day 7, reaching a steady state, and remaining constant up to day 21. Scores on psychopathology rating scales decreased; serum prolactin and neurological rating scale for extrapyramidal effects rose at day 7 and remained stable thereafter. No correlation was found between serum concentration values, including sum and ratio of RIS and 9-OH-RIS, and any of the other clinical values (serum prolactin and clinical scales). These data indicate that clinical changes are related to the achievement of steady state levels of RIS and its metabolite and are maintained, but not continued, with continued RIS treatment. Therapeutic drug monitoring of RIS and its metabolites is not recommended as a routine procedure in patients with psychotic disorders.
AB - The aim of this study was to assess a method able to analyze serum levels of risperidone (RIS) and its metabolite, 9-hydroxyrisperidone (9-OH-RIS), and to investigate possible relationships between changes in serum concentrations of these drugs and clinical measures, so to identify early markers of treatment response. The authors developed a sensitive and specific liquid chromatography-tandem mass spectrometry method to measure RIS and its metabolite in serum. Fifteen RIS-naive patients were admitted to an acute psychiatric care unit and treated with 4-6 mg/d oral RIS. At days 7 and 21 of hospital stay, serum levels were measured; clinical scales and serum prolactin were assessed. RIS and its metabolite were analyzed by a Q-Trap 2000 triple quadrupole/ion trap mass spectrometer in the multiple reaction-monitoring mode. Chromatographic separation was accomplished using a cyano column with an analytical run of 9 minutes. The calibration curve exhibited consistent linearity and reproducibility in the range 0-100 ng/mL for both analytes. Lower limit of quantification was 0.2 ng/mL; limit of detection, for a signal to noise ratio of 3, was 0.05 ng/mL for both analytes. Serum RIS and 9-OH-RIS levels increased at day 7, reaching a steady state, and remaining constant up to day 21. Scores on psychopathology rating scales decreased; serum prolactin and neurological rating scale for extrapyramidal effects rose at day 7 and remained stable thereafter. No correlation was found between serum concentration values, including sum and ratio of RIS and 9-OH-RIS, and any of the other clinical values (serum prolactin and clinical scales). These data indicate that clinical changes are related to the achievement of steady state levels of RIS and its metabolite and are maintained, but not continued, with continued RIS treatment. Therapeutic drug monitoring of RIS and its metabolites is not recommended as a routine procedure in patients with psychotic disorders.
KW - 9-hydroxyrisperidone
KW - LC-MS/MS
KW - Prolactin
KW - Risperidone
KW - Therapeutic drug monitoring
UR - http://www.scopus.com/inward/record.url?scp=68449091370&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68449091370&partnerID=8YFLogxK
U2 - 10.1097/FTD.0b013e3181aa4780
DO - 10.1097/FTD.0b013e3181aa4780
M3 - Article
C2 - 19531984
AN - SCOPUS:68449091370
VL - 31
SP - 475
EP - 481
JO - Therapeutic Drug Monitoring
JF - Therapeutic Drug Monitoring
SN - 0163-4356
IS - 4
ER -