Solid phase microextraction and LC–MS/MS for the determination of paliperidone after stereoselective fungal biotransformation of risperidone (original) (raw)
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Journal of Chromatography B, 2008
Two liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) methods are described, one for the quantitative determination of risperidone and the enantiomers of its active metabolite 9-hydroxyrisperidone (paliperidone) in human plasma and the other for the determination of the enantiomers of 9-hydroxyrisperidone in human urine. The plasma method is based on solid-phase extraction of 200 l of sample on a mixed-mode sorbent, followed by separation on a cellulose-based LC column with a 13.5-min mobile phase gradient of hexane, isopropanol and ethanol. After post-column addition of 10 mM ammonium acetate in ethanol/water, detection takes place by ion-spray tandem mass spectrometry in the positive ion mode. Method validation results show that the method is sufficiently selective towards the enantiomers of 7-hydroxyrisperidone and capable of quantifying the analytes with good precision and accuracy in the concentration range of 0.2-100 ng/ml. An accelerated (run time of 4.3 min) and equally valid method for the enantiomers of 9-hydroxyrisperidone alone in plasma is obtained by increasing the mobile phase flow-rate from 1.0 to 2.0 ml/min and slightly adapting the gradient conditions. The urine method is based on the same solid-phase extraction and chromatographic approach as the accelerated plasma method. Using 100 l of sample, (+)-and (−)-9-hydroxyrisperidone can be quantified in the concentration range 1-2000 ng/ml. The accelerated method for plasma and the method for urine can be used only when paliperidone is administered instead of risperidone, as there is insufficient separation of the 9-hydroxy enantiomers from the 7-hydroxy enantiomers, the latter ones being present only after risperidone administration.
International Journal of Biomedical Science : IJBS, 2013
A selective, sensitive and simple reversed-phase HPLC method for the determination of risperidone in bulk powder and pharmaceutical formulations was developed and validated. Risperidone can be separated on a Supelcosil LC8 DB column (250 mm × 4.6 mm i.d., 5 μm particle size) at 40°C with a mobile phase of methanol and 0.1 M ammonium acetate pH 5.50 (60:40, v/v), pumped at flow rate 1.0 mL min-1 and detected at 274 nm. Chlordiazepoxide hydrochloride was used as internal standard. The retention time of risperidone and chlordiazepoxide hydrochloride was found to be 5.89 and 7.65 min, respectively. The validation of the proposed method was carried out for specificity, linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The linear range was 4.0-275.0 µg mL-1 (r2=0.9998) with limits of detection and quantification values of 0.48 and 1.59 μg mL-1, respectively. The precision of the method was demonstrated using intra- and inter-day assay RSD values whi...
Medical Laboratory Technology Journal, 2022
Risperidone (RIS) is one of the most widely used atypical antipsychotics for treating schizophrenia in hospitals. RIS is metabolized by the liver and produces the primary active metabolite 9-OH-Risperidone (9-OHR). In the process of RIS metabolism, it is suspected that there are gene polymorphisms that cause variations in patient responses. Analysis of RIS and 9-OHR levels in the patient's blood can help to explain the various responses. High-Performance Liquid Chromatography (HPLC) is the most popular method to analyze RIS and 9-OHR, but many deficiencies were found in the chromatograms in the previous study. This research aims to obtain optimal conditions of the analysis prior to method validation. Condition optimization by optimizing the wavelength, composition of the mobile phase, pH, flow rate, and particle size of the stationary phase. The results showed that the wavelength was 279 nm, the mobile phase was 0.05 M KH2PO4 pH 3.7: acetonitrile (94:6, v/v) plus 0.3% triethyla...
2021
Background: Risperidone is an antipsychotic drug that is selective to dopamine D2 and serotonin 5-HT2A receptors and used in the management of schizophrenia, and bipolar mania. Aim: The work objective was to establish a specific, accurate, and sensitive analytical method for the quantification of risperidone in pharmaceutical dosage forms. The method will be used as a quality control tool for testing pre-market and post-market distribution of risperidone products, ensuring that the dosage forms are fulfilling the required labeled amount of the drug. Methods: Evaluation of risperidone in commercial pharmaceutical products administered in hospitals, community pharmacies, and other health care facilities by the development of a high-performance liquid chromatographic (HPLC) method to add a validated sensitive and selective method to literature methods. Results: The method showed specificity, sensitivity, and selectivity, and linearity (R 2 >0.999) within concentration range of 0.2 to 6 µg/mL for dissolution medium USP (0.1N HCl), and 0.1 to 3.4 µg/mL for dissolution medium pH1.2, 4.5, and 6.8. Accuracy percentage within 98-102%, and precision percentage below 2%. The mean recovery of assayed tablets is 100.113%. In addition, dissolution results meet the required 80% dissolution limit within 10 minutes. Conclusion: The developed analytical technique is fully validated and applicable for use in the quantitative analysis of risperidone.
PHARMACOKINETIC STUDY OF RISPERIDONE: APPLICATION OF A HPLC METHOD WITH SOLID PHASE EXTRACTION
Journal of the Chilean Chemical Society, 2011
A new, simplified solid phase extraction procedure for the determination of risperidone and 9-hydroxyrisperidone in human plasma has been developed. This method involves the use of an optimized extraction protocol developed in Waters OASIS ® HLB 30mg 1cc extraction columns using 1 mL of human serum. Separation was performed by HPLC using a Waters XTerra RP-18 (5 µm, 150x4,6 mm) column with a mobile phase consisting in acetonitrile -potassium dihydrogen phosphate 50 mM pH 3.4 (27/73). UV detection at 278 nm was used to quantify analytes, encountering good linearity (r 2 > 0.999) in the 2-100 ng/mL concentration range. The mean recovery was 92.4 % and 92.8 % for risperidone and 9-hydroxyrisperidone respectively, with an intraday -interday precision below 7%, and accuracy below 115 %. The method has been successfully applied in pharmacokinetic studies that require a large sample number.
Journal of Chromatography B, 2003
Since the first entry of risperidone on to the market in the early 1990s, investigation of the pharmacokinetic behaviour of the compound for which the availability of a bioanalytical method was a conditio sine qua non, has received considerable attention. Most of the published methods, however, did not reach the level of sensitivity and selectivity which can be obtained today since the evolution of liquid chromatography-tandem mass spectrometry (LC-MS-MS) towards a routine technique in the bioanalytical laboratory. Therefore, we developed and validated a new LC-MS-MS method for the determination of risperidone and its active metabolite 9-hydroxyrisperidone in human plasma. This paper describes in detail the bioanalytical procedure and summarizes the validation results obtained. In addition, it focuses on the pitfalls one might encounter when developing similar assays. Despite the particular physicochemical characteristics of risperidone and 9-hydroxyrisperidone, the LC-MS-MS method enabled the quantification of both compounds down to 0.1 ng / ml. The method uses a sample preparation step by solid-phase extraction at pH 6 using a mixed-mode phase. In a short chromatographic run, separation of 9-hydroxyrisperidone from the minor metabolite 7-hydroxyrisperidone is achieved. Detection takes place by (turbo)ionspray tandem mass spectrometry in the positive ion mode. The validated concentration range is from 0.100 to 250 ng / ml, using 500 ml of sample, with accuracy (bias) and precision (coefficient of variation) being below 15%. Although new developments in equipment will allow us to further improve and speed up the method, the assay reported can be used as a routine method to support a wide range of pharmacokinetic studies.
Determination of risperidone and enantiomers of 9-hydroxyrisperidone in plasma by LC-MS/MS
Journal of Chromatography B, 2007
A robust and validated liquid-liquid extraction LC-MS/MS method was developed for population pharmacokinetic analysis and therapeutic drug monitoring of risperidone and the enantiomers of its major active metabolite (+)-and (-)9-hydroxyrisperidone in pediatric patients. The method was rapid, sensitive and used a low sample amount (200 μL), which is very desirable for the pediatric population. The assay was validated from 0.2-50 ng/mL in plasma for all analytes. LLOQ for all analytes was 0.2 ng/mL. The extracts were analyzed by normal phase LC-MS/MS. The sample run time was 8 minutes. Intra-and interday precision for all analytes was ≤ 6 %; method accuracy was between 89 and 99 %. Additional experiments were performed to analyze matrix effects and identify a proper internal standard for each analyte. The validated method was used to study risperidone and its enantiomer metabolites in plasma as part of a population pharmacokinetic study in pediatric patients with pervasive developmental disorder (PDD).
Journal of Chromatography B: Biomedical Sciences and Applications, 2000
A simple and sensitive high-performance liquid chromatographic (HPLC) method with UV absorbance detection is described for the quantitation of risperidone and its major metabolite 9-hydroxyrisperidone in human plasma, using clozapine as internal standard. After sample alkalinization with 1 ml of NaOH (2 M) the test compounds were extracted from plasma using diisopropyl ether-isoamylalcohol (99:1, v / v). The organic phase was back-extracted with 150 ml potassium phosphate (0.1 M, pH 2.2) and 60 ml of the acid solution was injected into a C BDS Hypersil analytical column (3 mm, 10034.6 mm 18 I.D.). The mobile phase consisted of phosphate buffer (0.05 M, pH 3.7 with 25% H PO)-acetonitrile (70:30, v / v), and was 3 4 delivered at a flow-rate of 1.0 ml / min. The peaks were detected using a UV detector set at 278 nm and the total time for a chromatographic separation was about 4 min. The method was validated for the concentration range 5-100 ng / ml. Mean recoveries were 98.0% for risperidone and 83.5% for 9-hydroxyrisperidone. Intra-and inter-day relative standard deviations were less than 11% for both compounds, while accuracy, expressed as percent error, ranged from 1.6 to 25%. The limit of quantitation was 2 ng / ml for both analytes. The method shows good specificity with respect to commonly prescribed psychotropic drugs, and it has successfully been applied for pharmacokinetic studies and therapeutic drug monitoring.