Quantitative determination of risperidone, paliperidone and olanzapine in human serum by liquid chromatography-tandem mass spectrometry coupled with on-line solid-phase extraction.

A recent guideline recommends therapeutic drug monitoring for risperidone, paliperidone and olanzapine, which are frequently used second-generation antipsychotics. We developed a simple high-performance liquid chromatography-tandem mass spectrometry coupled with an online solid-phase extraction method that can be used to measure risperidone, paliperidone and olanzapine using small (40 μL) samples. The analytes were extracted from serum samples automatically pre-concentrated and purified by C8 (5 μm, 2.1 × 30 mm) solid-phase extraction cartridges, then chromatographed on an Xbidge™ C18 column (3.5 μm, 100 × 2.1 mm) thermostatted at 30°C with a mobile phase consisting of 70% acetonitrile and 30% ammonium hydroxide 1% solution at an isocratic flow rate of 0.3 mL/min, and detected with tandem mass spectrometry. The assay was validated in the concentration range from 2.5 to 160 ng/mL. Intra- and inter-day precision for all analytes was between 1.1 and 8.2%; method accuracy was between 6.6 and 7.6%. The risperidone and paliperidone assay was compared with a high-performance liquid chromatography-ultraviolet assay currently used in our hospital for risperidone and paliperidone therapeutic drug monitoring, and the results of weighted Deming regression analysis showed good agreement. For the olanzapine assay, we compared 20 samples in separate re-assays on different days; all the relative errors were within the 20% recommended limit.

Ruan CJ ，Guo W ，Zhou M ，Guo GX ，Wang CY ，Li WB ，de Leon J ... -  《-》

Concurrent determination of olanzapine, risperidone and 9-hydroxyrisperidone in human plasma by ultra performance liquid chromatography with diode array detection method: application to pharmacokinetic study.

A simple and sensitive ultra-performance liquid chromatography (UPLC) method has been developed and validated for simultaneous estimation of olanzapine (OLZ), risperidone (RIS) and 9-hydroxyrisperidone (9-OHRIS) in human plasma in vitro. The sample preparation was performed by simple liquid-liquid extraction technique. The analytes were chromatographed on a Waters Acquity H class UPLC system using isocratic mobile phase conditions at a flow rate of 0.3 mL/min and Acquity UPLC BEH shield RP18 column maintained at 40°C. Quantification was performed on a photodiode array detector set at 277 nm and clozapine was used as internal standard (IS). OLZ, RIS, 9-OHRIS and IS retention times were found to be 0.9, 1.4, .1.8 and 3.1 min, respectively, and the total run time was 4 min. The method was validated for selectivity, specificity, recovery, linearity, accuracy, precision and sample stability. The calibration curve was linear over the concentration range 1-100 ng/mL for OLZ, RIS and 9-OHRIS. Intra- and inter-day precisions for OLZ, RIS and 9-OHRIS were found to be good with the coefficient of variation <6.96%, and the accuracy ranging from 97.55 to 105.41%, in human plasma. The validated UPLC method was successfully applied to the pharmacokinetic study of RIS and 9-OHRIS in human plasma.

Siva Selva Kumar M ，Ramanathan M 《-》

Long-term stability of five atypical antipsychotics (risperidone, olanzapine, paliperidone, clozapine, quetiapine) and the antidepressant mirtazapine in human serum assessed by a validated SPE LC-MS/MS method.

Fruekilde PBN ，Nielsen F 《-》

Development of a rapid and sensitive SPE-LC-MS/MS method for the simultaneous estimation of fluoxetine and olanzapine in human plasma.

A high-performance liquid chromatographic assay with tandem mass spectrometric detection was developed to simultaneously quantify fluoxetine and olanzapine in human plasma. The analytes and the internal standard (IS) duloxetine were extracted from 500 μL aliquots of human plasma through solid-phase extraction. Chromatographic separation was achieved in a run time of 4.0 min on a Hypersil Gold C₁₈ column (50 × 4.6 mm, 5 µm) using isocratic mobile phase consisting of acetonitrile-water containing 2% formic acid (70:30, v/v), at a flow-rate of 0.5 mL/min. Detection of analytes and internal standard was performed by electrospray ionization tandem mass spectrometry, operating in positive-ion and multiple reaction monitoring acquisition mode. The protonated precursor to product ion transitions monitored for fluoxetine, olanzapine and IS were m/z 310.01 → 147.69, 313.15 → 256.14 and 298.1 → 153.97, respectively. The method was validated over the concentration range of 1.00-150.20 ng/mL for fluoxetine and 0.12-25.03 ng/mL for olanzapine in human plasma. The intra-batch and inter-batch precision (%CV) across four quality control levels was ≤ 6.28% for both the analytes. In conclusion, a simple and sensitive analytical method was developed and validated in human plasma. This method is suitable for measuring accurate plasma concentration in bioequivalence study and therapeutic drug monitoring as well, following combined administration.

Gopinath S ，Kumar RS ，Alexander S ，Danabal P ... -  《-》

A water-compatible magnetic molecularly imprinted polymer for the selective extraction of risperidone and 9-hydroxyrisperidone from human urine.

An accurate, rapid, and sensitive method for the determination of risperidone and 9-hydroxyrisperidone in urine samples was developed by combining water-compatible magnetic molecularly imprinted solid-phase extraction with high performance liquid chromatography. Several variables relating to the efficiency of magnetic solid phase extraction were optimized, including the amount of adsorbent, adsorption time, type of elution solvent, and desorption time. The analytical performance of this method was validated under the optimized conditions. The linearity for risperidone and 9-hydroxyrisperidone was obtained in the range 1-2000ngmL-1 with correlation coefficient ≥ 0.991. Limits of detection of risperidone and 9-hydroxyrisperidone are 0.21ngmL-1 and 0.24ngmL-1, respectively. Recoveries at three spike levels (10, 100, and 1000ngmL-1) ranged from 94.6% to 102.4% with relative standard deviations (%) ≤ 5.3. These results confirmed that this method can be successfully and facilely used to analyze the multi-residues of risperidone and 9-hydroxyrisperidone in urine samples with high efficiency and good sensitivity.

Ji WH ，Guo YS ，Wang X ，Guo DS ... -  《-》