Sensitive liquid chromatography/tandem mass spectrometry method for the simultaneous determination of olanzapine, risperidone, 9-hydroxyrisperidone, clozapine, haloperidol and ziprasidone in rat brain tissue

Abstract

One prerequisite for therapeutic effects of psychiatric drugs is the ability to pass the blood brain barrier. Hence, it is important to know the concentration of antipsychotic drugs in brain tissue. In general, determinations of lipophilic compounds from lipophilic matricies such as the brain are a challenge. Here we have adapted a plasma assay for antipsychotics for the target organ the brain. Using modified sample preparation and chromatographic strategies, the analytes were extracted from rat brain homogenate and analyzed by LC-MS/MS. The method used a Waters Atlantis dC-18 (30 mm x 2.1 mm i.d., 3 microm) column with a mobile phase of acetonitrile/5 mM ammonium formate (pH 6.1 adjusted with formic acid) and gradient elution. All analytes were detected in positive ion mode using multiple-reaction monitoring. The method was validated and the linearity, lower limit of quantitation, precision, accuracy, recoveries, specificity and stability were determined. This method was then successfully used to quantify the rat brain tissue concentration of the analytes after chronic treatment with these antipsychotic drugs.

Screening and quantification of antipsychotic drugs in human brain tissue by liquid chromatography–tandem mass spectrometry: Application to postmortem diagnostics of forensic interest

“…Beyond this time period that stability is not guaranteed because it was found that after 48 h the concentrations of olanzapine in the QCs were reduced to 95.3%. This result is in agreement with the findings of other authors [12,23], which reported that vitamin C can be added to the brain homogenate to prevent olanzapine degradation. For this reason, calibration brain eluates were freshly prepared and analyzed on the same day in this study,…”

“…There are numerous reports of using LC-MS methods for the determination of some of these compounds in plasma [13,14], serum [15], blood [16,17], urine [18], cerebrospinal fluid [19], hair [20][21][22] and rat brain tissue [23]. However, to date, LC-MS/MS methods for the simultaneous screening and determination of the 17 most commonly used antipsychotic drugs, have not been developed.…”

Neural Network Ensemble Based QSAR Model for the BBB Challenge: A Review

“…This is due to the fuzzy nature of measurement and lack of persistence. For example, plasma to brain ratio of Clozapine (Clozaril) appears as 24 [32], or 4.1 [33], which is a large gap. Therefore it was decided that the drugs will be divided into four permeability groups in the range 1-4 where 1 is the least permeable drug, and 4 is the most.…”

Development of a Novel High-Throughput Analytical Methodology, Multiple Injection Method, for Quantitative Analysis in Drug Metabolism and Pharmacokinetic Studies Using Liquid Chromatography with Tandem Mass Spectrometry

“…Under the fed condition, 10 mg/kg of fexofenadine and verapamil, 20 mg/kg of risperidone, 2 mg/kg of ondansetron, and 30 mg/kg of imipramine were orally administrated to rats by gavage (nϭ2/compound). [19][20][21][22][23][24][25][26] The volume of a dose of the 0.5% methylcellulose suspension was 2 ml/kg for each model compound. Blood samples (200 ml) were collected at 0.25, 0.5, 1, 2, and 6 h after oral administration.…”