title: MultiSimplex optimization of chromatographic separation and dansyl derivatization conditions in the ultra performance liquid chromatography-tandem mass spectrometry analysis of risperidone, 9-hydroxyrisperidone, monoamine and amino acid neurotransmitters in human urine.
abstract: A pre-column dansylated ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of risperidone (RIP), 9-hydroxyrisperidone (9-OH-RIP), monoamine and amino acid neurotransmitters in human urine was developed with the aim of providing data on how neurotransmitters may influence each other or change simultaneously in response to risperidone treatment. MultiSimplex based on the simplex algorithm and the fuzzy set theory was applied to the optimization of chromatographic separation and dansyl derivatization conditions during method development. This method exhibited excellent linearity for all the analytes with regression coefficients higher than 0.997. The lower limit of quantification (LLOQ) values for 9-OH-RIP and RIP were 0.11 and 0.06 ng/ml, respectively, and for neurotrasmitters ranged from 0.31 to 12.8 nM. The mean accuracy ranged from 94.7% to 108.5%. The mean recovery varied between 81.6% and 97.5%. All the RSD of precision and stability were below 9.7%. Finally, the optimized method was applied to analyze the first morning urine samples of schizophrenic patients treated with risperidone and healthy volunteers.
authors.affiliation: Clinical Pharmacy & Pharmacology Research Institute, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, PR China.
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Cai
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Zhu
authors.forename: Huan-De
authors.initials: HD
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Lan-Fang
authors.initials: LF
authors.lastname: Li
mesh_terms: D015306:Biogenic Monoamines / Q000652:urine*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003619:Dansyl Compounds / Q000737:chemistry; D006801:Humans; D007555:Isoxazoles / Q000652:urine*; D015999:Multivariate Analysis; D018377:Neurotransmitter Agents / Q000652:urine*; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000652:urine*; D015203:Reproducibility of Results; D018967:Risperidone / Q000652:urine*; D012559:Schizophrenia / Q000188:drug therapy / Q000652:urine; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D015306:Biogenic Monoamines; D003619:Dansyl Compounds; D007555:Isoxazoles; D018377:Neurotransmitter Agents; D011743:Pyrimidines; D018967:Risperidone; C029038:dansyl chloride; D000068882:Paliperidone Palmitate