Quantification Of Olanzapine Research Articles

LC-MS/MS quantification of olanzapine in hair after alkaline digestion.

Olanzapine (OLZ), a second-generation antipsychotic drug, is effective in the treatment of acute psychosis, schizophrenia, agitation, bipolar mania, and other psychiatric problems. Antipsychotics are prescribed drugs, which lead the drug abuser to illegal methods of access. This behavior also demonstrates the association of OLZ with criminal involvement, commonly observed at forensic crime scenes. The acute toxicity and even death resulting from OLZ exposure have been highlighted in numerous studies. Therefore, developing analytical techniques to detect OLZ is essential for forensic toxicology. This study aimed to develop a specific and reliable LC-MS/MS method for OLZ detection and quantification in hair samples. The method was validated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), trueness, precision, and uncertainty. The range of linearity was between 0.1-100 ng/mg, with LOD and LOQ values established at 0.036 ng/mg and 0.1ng/mg, respectively. All validation results are within acceptable parameters. The validated method has been applied to authentic hair samples. The variation of OLZ concentrations in 12 hair segments (2 from Case 1 and 10 from Case 2) from two drug-positive patients, ranging from 0.131 to 0.460 ng/mg, is presented in this study. Although several studies have been conducted to determine OLZ in hair samples using segmental analysis via hair solubilization, this study is the first to determine OLZ in hair samples after "digestion" with comparative parameters prior to chromatographic analysis.

A Review of Advances in Bioanalytical Methods for the Detection and Quantification of Olanzapine and Its Metabolites in Complex Biological Matrices.

Schizophrenia is a serious mental disorder that significantly affects the social and professional life of patients, causing distortion of reality and loss of identity and cognitive abilities. Psychopharmacological treatment is an integral part of modern psychiatry, and the introduction of new "atypical" antipsychotic drugs has brought significant progress in the treatment of this disorder. One of these drugs is olanzapine, which has an effective effect on the productive symptoms of schizophrenia while having an almost minimal potential to cause extrapyramidal syndrome. However, its effectiveness is confronted with frequent side effects, referred to as "metabolic disorders". Therefore, to ensure the effectiveness of treatment and to minimize the side effects caused by olanzapine, it is recommended to monitor the drug level during therapy. This article reviews the bioanalytical methodologies that enable efficient extraction and sensitive analysis of olanzapine. We considered the advantages and disadvantages of different sample pretreatment methods, including traditional and novel strategies. The analytical conditions required for the separation and detection of olanzapine and its metabolites were analyzed using chromatographic methods combined with various detectors.

Quantification of Olanzapine by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Olanzapine (Zyprexa™) is indicated for the treatment of schizophrenia and bipolar disorder. Olanzapine is metabolized to inactive metabolites; therefore, this assay measures the concentrations of olanzapine and internal standard, olanzapine-D3. This procedure provides instructions for quantitating levels of olanzapine in blood serum specimens. An internal standard (IS) solution consisting of the deuterated analogue of olanzapine is added to an aliquot of the patient serum or plasma, standards, and positive controls. The drugs of interest are separated from the biological fluid using solid phase extraction. The dried extracts are reconstituted in mobile phase and separated by liquid chromatography. The solution is introduced into an Agilent 6470A triple quadrupole tandem mass spectrometer via positive mode electrospray ionization (ESI) utilizing multiple reaction monitoring (MRM). Quantitation is performed by comparison to a calibration curve, using Indigo® (Ascent) software.

Quantification of olanzapine and its three metabolites by liquid chromatography–tandem mass spectrometry in human body fluids obtained from four deceased, and confirmation of the reduction from olanzapine N-oxide to olanzapine in whole blood in vitro

PurposeQuantification of olanzapine (OLZ) and its metabolites such as N-desmethylolanzapine (DM-O), 2-hydroxymethylolanzapine (2H-O) and olanzapine N-oxide (NO-O) in five kinds of human body fluids including whole blood by liquid chromatography (LC)–tandem mass spectrometry (MS/MS) has been presented; the quantification methods were carefully devised and validated using the matrix-matched calibration and standard addition methods.MethodsOLZ and its three metabolites were extracted from 40 μL each of body fluids by two-step liquid–liquid separations. The samples and reagents were pre-cooled in a container filled with ice for the extraction because of the thermal instability of OLZ and its three metabolites especially in whole blood.ResultsThe limits of quantification (LOQs) of OLZ and 2H-O were 0.05 ng/mL and those of DM-O and NO-O were 0.15 ng/mL in whole blood and urine, respectively. The concentrations of OLZ and its metabolites in heart whole blood, pericardial fluid, stomach contents, bile and urine were determined for two cadavers and those in whole blood and urine for the other two cadavers. The reduction from NO-O to OLZ was observed at 25 ℃ in whole blood in vitro.ConclusionsTo our knowledge, this is the first report on the quantification of metabolites of olanzapine in the authentic human body fluids by LC–MS/MS as well as on the confirmation of in vitro reduction from NO-O to OLZ in whole blood that seems to have induced the quick decrease of NO-O.

Reference Brain and Blood Concentrations of Olanzapine in Postmortem Cases.

The antipsychotic drug olanzapine may be subject to postmortem redistribution. This complicates the toxicological evaluation in postmortem cases and a supplementary analysis of brain tissue may be an advantage. We report reference brain and blood concentrations of olanzapine from 40 forensic autopsy cases. Each case was assigned to one of three groups according to the cause of death: (A) fatal intoxication by olanzapine alone; (B) fatal intoxication by olanzapine in combination with other drugs and (C) olanzapine was not related to the cause of death. Quantification of olanzapine in brain and blood was performed by ultra-performance liquid chromatography with tandem mass spectrometry using a validated method. A linear correlation between concentrations in blood and brain from 40 cases was found with a correlation coefficient of 0.87. The median brain:blood ratio was 2.5 (10-90%: 1.2-5.8, range: 0.72-10.4). For the A cases (n = 2), the concentrations in brain (Br) and femoral blood (FB) were: Br: 2.1-3.6 mg/kg, FB: 0.99-1.2 mg/kg; for the B cases (n = 17) the 10-90% were: Br: 0.27-1.0 mg/kg (range: 0.13-1.3 mg/kg) FB: 0.11-0.57 mg/kg (range: 0.096-0.65 mg/kg) and the 10-90% of the C cases (n = 21): Br: 0.05-0.49 mg/kg (range: 0.040-0.87 mg/kg) FB: 0.02-0.14 mg/kg (range: 0.008-0.15 mg/kg). These results can serve as reference concentrations for the interpretation of postmortem forensic cases.

Determination of Olanzapine in Pharmaceutical Preparations by Linear Sweep Voltammetry Method

In this study, simple and fast linear sweep voltammetry method was developed and validated for determination of olanzapine in pharmaceutical preparations. The proposed method was based on electrochemical oxidation of olanzapine on glassy carbon electrode in solution containing 0.04 M Britton-Robinson buffer of pH 1.65. The well-defined an oxidation peak was observed at 1.06 V. The calibration curve was linear for olanzapine at the concentration range of 2.5-50 µg/mL for linear sweep voltammetry method. Intra- and inter-day precision values for olanzapine were less than 4.78, and accuracy (relative error) was better than 1.85%. The limits of detection and quantification of olanzapine were 0.50 and 1.50 μg/mL, respectively. The mean recovery of olanzapine was 99.8% for pharmaceutical preparations. Stability measurements were carried out with linear sweep voltammetry method. The results were evaluated comparing these measurements with those of standards and expressed as percentage deviation and olanzapine was found as stable at room temperature, 4 and -20 °C for at least 72 h. No interference was found excipient at the selected assay conditions. The voltammetric run time of 1 min allows the analysis of a large number of samples in a short period of time. The proposed method is highly sensitive, precise and accurate and can be used for the reliable quantitation of olanzapine in pharmaceutical dosage form

The Use of Near Infrared Spectroscopy and Multivariate Calibration for Determining the Active Principle of Olanzapine in a Pharmaceutical Formulation

The aim of this study was to quantitatively determine the olanzapine in a pharmaceutical formulation for assessing the potentiality of near infrared spectroscopy (NIR) combined with partial least squares (PLS) regression. The method was developed with samples based on a commercial formulation containing olanzapine and seven excipients. Laboratory and commercial samples (n = 27 and 18, respectively) were used by defining the calibration and prediction sets. The method was validated in the range from 1.0 to 12.5 of olanzapine per 100 mg of powder (average mass 210 mg), by accuracy, precision, linearity, analytical sensitivity, limit of detection and quantification. The multivariate model developed for olanzapine was based on PLS and the determination coefficient (rc and rp), with the root mean square error of calibration and prediction being 0.95, 0.93, 3.2 × 10-3 and 4.0 × 10-3% m/m, respectively. The proposed NIR method is an effective alternative for quantification of olanzapine in the pharmaceutical industry.

Development and Validation of an HPTLC Method for Determination of Olanzapine in Formulations

A new, simple, and rapid HPTLC method was developed and validated for quantitative determination of olanzapine on silica gel 60F254 layers using methanol-ethyl acetate (8.0 + 2.0, v/v) as the mobile phase. Olanzapine was quantified by densitometric analysis at 285 nm. The method was found to give compact bands for the drug (Rf = 0.35 +/- 0.02). The linear regression analysis data for the calibration plots showed a good linear relationship with r2 = 0.9997 in the concentration range of 100-600 ng/band. The method was validated for precision, recovery, repeatability, and robustness as per the International Conference on Harmonization guidelines. The LOD was found to be 23.90 ng/band, and the LOQ was 91.04 ng/band. Statistical analysis of the data showed that the method is precise, accurate, reproducible, and selective for the analysis of olanzapine. The method was successfully used for the determination of equilibrium solubility and quantification of olanzapine as a bulk drug, in a commercially available preparation, and in in-house developed mucoadhesive microemulsion formulations and solution.