ABSTRACT
OBJECTIVE:To establish the method for simultaneous determination of risperidone (RIS) and 9-hydroxyrisperi-done (9-OH-RIS) in human plasma. METHODS:After liquid-liquid extraction of plasma sample,using AF2672 as internal stan-dard(IS),LC-MS/MS was adopted. The determination was performed on XtimateTM C18 column with mobile phase consisted of ace-tonitrile-10 mmol/L ammonium acetate solution(containing 0.1％ formic acid)(37:63,V/V,pH=3.2)at the flow rate of 0.25 mL/min. The column temperature was 40 ℃,and the sample size was 6 μL. The ESI was equipped and quantitative analysis was operated in positive ion and MRM mode. The mass transition ion-pairs were followed as m/z 411.26→191.02 for RIS,m/z 427.21→206.91 for 9-OH-RIS and m/z 418.00→175.95 for IS. RESULTS:The linear range of RIS was 0.2-50.0 ng/mL(r=0.9997)and 9-OH-RIS was 1.0-200.0 ng/mL (r=0.9987). RSDs of inter-day and intra-day were all lower than 15％,and the method recoveries were 92.42％-104.81％ and 94.51％-100.57％;matrix effects were 98.33％-107.09％ and 91.05％-105.80％;extraction recoveries were 78.11％-92.62％ and 76.32％-85.09％,respectively. The plasma concentrations of RIS and 9-OH-RIS in 78 schizophrenic patients were(13.58±8.31)and(25.62±15.52)ng/mL. CONCLUSIONS:The developed method is simple,sensitive and specific,which is suitable for routine drug monitoring and acute toxic analysis in patients receiving risperidone.
ABSTRACT
OBJECTIVE:To discuss the correlation between multidrug resistance gene (MDR1) polymorphisms and plasma concentration of risperidone,9-hydroxyrisperidone and total active substance in Han patients with schizophrenia. METHODS:78 Han inpatients with schizophrenia in Mental Health Institute of Second Xiangya Hospital of Central South University from Dec. 2011 to Jan. 2013 were selected,LC-MS/MS was conducted to determine the plasma concentration of risperidone,9-hydroxyrisperi-done and total active substance,PCR-LDR was adopted to determine the genotyping of C1236T,G2677T and C3435T of patients, and one-way ANOVA was used to detect the correlation between C1236T,G2677T and C3435T polymorphisms and plasma concen-tration/dose calibration ratio (C/D) value of risperidone,9-hydroxyrisperidone and total active substance. RESULTS:The average plasma concentrations of risperidone,9-hydroxyrisperidone and total active substance for 78 patients were(13.58±8.31),(25.62± 15.52)and(39.24±25.76)ng/ml,respectively;the distribution frequencies of C1236T,G2677T and C3435T met the Hardy-Wein-berg equilibrium(P>0.05);the risperidone C/D value of patients with C12367T CT and TT genotype were higher than those with CC genotype,risperidone and total active substance C/D values of patients with G2677T TT genotype were higher than those with GG genotype,the differences were statistically significant (P0.05). CONCLUSIONS:The MDR1 C1236T and G2677T polymorphisms are associated with plasma concentration of risperidone and total active substance in Han patients with schizophrenia.
ABSTRACT
OBJECTIVE: Although antipsychotic polypharmacy is widely used in the pharmacotherapy of schizophrenia, its effectiveness is controversial. In particular, clinicians tend to avoid switching to monotherapy in patients who have been prescribed polypharmacy. In the present study, the authors investigate whether there is difference in time to discontinuation of antipsychotics between patients on previous monotherapy or polypharmacy. METHODS: Pooled analysis was conducted on two 24-week, multicenter, open-label, non-comparative studies that were originally designed to investigate the effectiveness of switching to paliperidone extended-release (ER) in patients with schizophrenia. Patients were divided into two groups according to previously prescribed antipsychotics, that is, to a polypharmacy group or a monotherapy group. The primary outcome measure was time to discontinuation of paliperidone ER. In addition, the authors sought to identify clinical variables that influence time to discontinuation. RESULTS: Before switching to paliperidone ER, 535 of 673 (79.5%) patients were prescribed antipsychotic monotherapy, and the remaining 138 (20.5%) patients were prescribed antipsychotic polypharmacy. No significant differences in time to discontinuation of paliperidone ER were observed between the polypharmacy and monotherapy groups. Personal and social performance scale score was the only factor found to influence time to discontinuation of paliperidone ER. No differences in psychopathology or adverse effects were found between the monotherapy and polypharmacy groups. CONCLUSION: Our results suggest that number of antipsychotics prescribed before switching to monotherapy does not influence clinical prognosis in patients with schizophrenia.