Abstract
Simultaneous quantification of multiple psychiatric drugs is important for the therapeutic drug monitoring of psychiatric patients. In addition, it would be highly advantageous if the method could be simple, straightforward, and not time-consuming. A 200 µl plasma sample was deproteinized, drugs were separated by a ZORBAX Eclipse XDB-Phenyl column with the mobile phase composed of acetonitrile and 0.1 % formic acid in water (60:40, v/v), and recorded in the MRM mode by using a positive electrospray source with tandem mass spectrometry detection. The dynamic range was 2–256 ng/ml for all the analyzed drugs, except escitalopram (8-256 ng/ml). Quality control samples were prepared in quintuplicates in three relevant concentrations for each drug. Coefficients of determination (R2) were higher than 0.99, while the relative difference between nominal and measured concentrations (RE) and CV were lower than 15% for all targets. High performance liquid chromatography coupled with the mass detector (HPLC-MS/MS) method for simultaneous determination of sertraline, escitalopram, risperidone and paliperidone in human plasma was validated with respect to selectivity, linearity, accuracy, precision, matrix effect and stability. This method has significant advantages in terms of low sample volume (200 µl), short preparation time (3 hours) and short runtime per sample (4 minutes).
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References
Kessler RC, Wang PS. The descriptive epidemiology of commonly occurring mental disorders in the United States. Annu Rev Public Health. 2008;29:115-29.
Leucht S, Crippa A, Siafis S, Patel MX, Orsini N, Davis JM. Dose-response meta-analysis of antipsychotic drugs for acute schizophrenia. Am J Psychiatry. 2020;177(4):342-53.
Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013; 382(9896):951-62.
Milosavljevic F, Bukvic N, Pavlovic Z, Miljevic C, Pešic V, Molden E, et al. Association of CYP2C19 and CYP2D6 Poor and Intermediate Metabolizer Status With Antidepressant and Antipsychotic Exposure: A Systematic Review and Meta-analysis. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2020.3643.
Heimke C. Concentration-Effect Relationships of Psychoactive Drugs and the Problem to Calculate Therapeutic Reference Ranges. Ther Drug Monit. 2019;41(2):174-9.
Jukic MM, Haslemo T, Molden E, Ingelman-Sundberg M. Impact of CYP2C19 Genotype on Escitalopram Exposure and Therapeutic Failure: A Retrospective Study Based on 2,087 Patients.Am J Pcychiatry. 2018;175(5):463-70.
Bråten LS, Haslemo T, Jukic MM, Ingelman-Sundberg M, Molden E, Kringen MK. Impact of CYP2C19 genotype on sertraline exposure in 1200 Scandinavian patients. Neuropsychopharmacology. 2020;45(3):570-6.
Jukic MM, Smith RL, Haslemo T, Molden E, Ingelman-Sundberg M. Effect of CYP2D6 genotype on exposure and efficacy of risperidone and aripiprazole: a retrospective, cohort study.Lancet Psychiatry. 2019;6(5):418-26.
Choong E, Rudaz S, Kottelat A, Guillarme D Veuthey JL Eap CB. Therapeutic drug monitoring of seven psychotropic drugs and four metabolites in human plasma by HPLC-MS. Pharm. Biomed. Anal. 2009;50(5):1000-8.
Kirchherr H, Kuhn-Velten WN. Quantitative determination of forty-eight antidepressants and antipsychotics in human serum by HPLC tandem mass spectrometry: a multi-level, single-sample approach. J Chromatogr B Analyt Technol Biomed Life Sci. 2006;843(1):100-13.
Juan H, Zhiling Z, Huande L. Simultaneous determination of fluoxetine, citalopram, paroxetine, venlafaxine in plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI). J Chromatogr B Analyt Technol Biomed Life Sci. 2005;820(1):33-9.
Zhou Z, Li X, Li K, Xie Z, Cheng Z, Peng W et al. Simultaneous determination of clozapine, olanzapine, risperidone and quetiapine in plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry J Chromatogr B Analyt Technol Biomed Life Sci. 2004;802(2):257-6.
Jiang KT, Rong Z, Peng L, Chen B, Xie Y, Chen C, et al. Simultaneous determination of citalopram and its metabolite in human plasma by LC–MS/MS applied to pharmacokinetic study. Journal of Chromatography B. 2010;878(5-6):615–9.
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