Determination Of Olanzapine Research Articles

Spectrophotometric Determination of Olanzapine by Charge-Transfer Complex Formation in its Pure Form and Pharmaceutical Formulations

Spectrophotometric Determination of Olanzapine by Charge-Transfer Complex Formation in its Pure Form and Pharmaceutical Formulations

A new selective carbon paste electrode for potentiometric analysis of olanzapine

A novel and very sensitive potentiometric sensor with excellent electrochemical properties containing olanzapine- tungstophosphate ion pair as modifier was fabricated for the analysis of olanzapine in real samples. The modified electrode showed Nernstian slope of 59.2 mV decade−1 for olanzapine concentration from 7.5 × 10−7 to 5.6 × 10−4 M and a limit of detection 5.0 × 10−7 M, showing high selectivity. Temperature dependence of the electrode potential response was examined in the temperature range of 15–55 °C, revealing a good thermal stability. Also, it showed a short and at least 2 months stable response of 4 s. The modified electrode was used to the study of the interaction between olanzapine drug and β-cyclodextrin and the relevant binding constant was determined. The electrode was used in the potentiometric titration of different olanzapine concentrations with phosphotungstic acid and also determination of olanzapine in real samples such as olanzapine tablet and human blood serum.

Determination of Olanzapine in Five Different Pharmaceutical Formulations by LC-MS Method

Determination of Olanzapine in Five Different Pharmaceutical Formulations by LC-MS Method

Spectrophotometric Determination of Olanzapine in the Presence of its Acidic Degradation Product; Application of Kinetic Study

Simple, accurate, selective and sensitive UV spectrophotometric methods have been developed and validated for the determination of olanzapine (OLZ) in presence of its acidic degradation product without preliminary separation. These methods include ratio subtraction, absorbance subtraction and amplitude modulation methods. Ratio subtraction method was used to study the kinetic of OLZ acidic degradation that was found to follow a pseudo-first-order reaction. The t1/2 was 4.91 hours while k (reaction rate constant) was 0.1411h-1. These methods were based on extension region of the degradation product. All the proposed methods were validated and successfully applied for determination of OLZ in Olanza® 5 mg tablets. The obtained results were statistically compared with those of the reported method by applying t-test and F-test at 95% confidence level and no significant difference was observed regarding accuracy and precision.

Kinetic Spectrophotometric and Spectrofluorimetric Methods for the Analysis of Olanzapine Using4-chloro-7-nitrobenzofurazan

Simple, accurate, sensitive and low cost spectrophotometric and spectrofluorimetric methods were developed for the determination of olanzapine (OLZ) using 4 chloro 7 nitrobenzofurazan (NBD-Cl) associated with kinetic study, either in pure form or in pharmaceutical preparation. In this work, OLZ was determined after reaction with NBD-Cl in the presence of 0.1M sodium bicarbonate at 90°C for 30 minutes. The reaction product was measured spectrophotometrically at 463 nm or spectrofluorimetrically at 540 nm after excitation at 460 nm. The calibration curves were linear in the range of 1-5.5 μg/mL using spectrophotometric method and 0.1-0.55 μg/ mL when spectrofluorimetric method was applied. The methods were applied successfully for commercial dosage form. The obtained results were statistically agreed with those obtained by the reported method. Kinetic determination of OLZ by rate constant and the fixed concentration methods was carried out, but the fixed time method proves to be more applicable.

DEVELOPMENT OF METHODS OF ANALYSES OF THE CLOZAPINE, RISPERIDONE, OLANZAPINE, SERTINDOLE, ARIPIPRAZOLE AND HALOPERIDOL IN THE MODEL MIXTURE OF URINE

Background. Uncontrolled use of atypical antipsychotics, and their combination with other drugs is the cause of acute domestic intoxication, poisoning and suicide. For rapid diagnosis of poisoning and the rational use of methods of detoxification is necessary to develop the methods of analysis in biological fluids clozapine, risperidone, olanzapine, sertindole, aripiprazole, haloperidol in the joint presence. Materials and methods. We were preparing a model mixture of urine with the content of the studied substances that meet their minimum therapeutic dose. Conducted three times extraction of mixture of butyl acetate: butanol (9:1) at pH=10. The substance was found by TLC. Analyte quantitatively determined by capillary electrophoresis. Results. The maximum separation of mixtures studied substances is observed in the system of methanol - 25% ammonia solution (100: 1,5). The linear range of the proposed method for simultaneous determination of clozapine, risperidone, aripiprazole was in the range of 4,0-80,0 mcg/ml, sertindole - in the range of 5,0 - 40 mcg/ml and olanzapine - in the range of 1,0 to 20,0 g/ml. Otkryvaet 99,8-100,5%, with a recurrence rate of 1,3% and 8,6%, intermediate precision - 1,8-11,5%. Variability does not exceed 3%. Total deviation was within acceptable limits ± 5%. Conclusion. Developed methods of detection and quantitative determination of olanzapine, clozapine, risperidone haloperidol, sertindole, aripiprazole in the model mixture of urine can be used for therapeutic drug monitoring and pharmacokinetic studies.

HPLC determination of olanzapine and carbamazepine in their nicotinamide cocrystals and investigation of the dissolution profiles of cocrystal tablet formulations

Cocrystals have recently gained importance in the pharmaceutical industry. In this study, olanzapine and carbamazepine cocrystals were synthesized by using nicotinamide as cocrystal forming agent to achieve improvements in the physicochemical characteristics of the active ingredients. An HPLC method was developed to determine the amount, thus, the stoichiometric ratios of olanzapine and carbamazepine in the synthesized cocrystals. Olanzapine:nicotinamide and olanzapine tablet formulations were prepared and the developed HPLC method was applied successfully in order to compare the dissolution profiles of these formulations. An ACE 5 CN, 25 cm × 4.6 mm, 5 µm column was used and a gradient elution program was performed for simultaneous determination of olanzapine, carbamazepine and nicotinamide. Phosphate buffer (pH 5.0, 25 mM) and methanol was used in a ratio from 80:20 to 70:30 while the flow rate was 1 mL min−1 for the elution of the compounds within 12 min. In conclusion, two different aims were achieved, the first one was to indicate the stoichiometric ratios of the active ingredients olanzapine and carbamazepine with nicotinamide in their cocrystals, and the second one was the comparison of the dissolution profiles of the olanzapine and olanzapine:nicotinamide cocrystal formulations. It was found that the cocrystal formulation with nicotinamide improved the dissolution profile of olanzapine.

Determination of Olanzapine and N-desmethyl-olanzapine in Plasma Using a Reversed-Phase HPLC Coupled with Coulochemical Detection: Correlation of Olanzapine or N-desmethyl-olanzapine Concentration with Metabolic Parameters

BackgroundOlanzapine (OLZ) is one of the most prescribed atypical antipsychotic drugs but its use is associated with unfavorable metabolic abnormalities. N-desmethyl-olanzapine (DMO), one of the OLZ metabolites by CYP1A2, has been reported to have a normalizing action on metabolic abnormalities, but this remains unclear. Our aim was to explore the correlation between the concentrations of OLZ or DMO with various metabolic parameters in schizophrenic patients.MethodsThe chromatographic analysis was carried out with a solvent delivery system coupled to a Coulochem III coulometric detector to determine OLZ and DMO simultaneously in OLZ-treated patients. The correlation between the concentration of OLZ or DMO and the metabolic parameters was analyzed by the Spearman rank order correlation method (r s).Principal FindingsThe established analytical method met proper standards for accuracy and reliability and the lower limitation of quantification for each injection of DMO or OLZ was 0.02 ng. The method was successfully used for the analysis of samples from nonsmoking patients (n = 48) treated with OLZ in the dosage range of 5–20 mg per day. There was no correlation between OLZ concentrations and tested metabolic parameters. DMO concentrations were negatively correlated with glucose (r s = –0.45) and DMO concentrations normalized by doses were also negatively correlated with insulin levels (r s = –0.39); however, there was a marginally positive correlation between DMO and homocysteine levels (r s = +0.38).ConclusionsThe observed negative correlations between levels of DMO and glucose or insulin suggest a metabolic normalization role for DMO regardless of its positive correlation with a known cardiovascular risk factor, homocysteine. Additional studies of the mechanisms underlying DMO’s metabolic effects are warranted.

Sensitive Liquid Chromatography–Tandem Mass Spectrometry Method for the Determination of Olanzapine in Human Urine

A sensitive and selective liquid chromatographic-tandem mass spectrometric (LC–MS–MS) method was developed to determine olanzapine (OLZ) in human urine. After solid-phase extraction with SPE cartridge, the urine sample was analysed on a C18 column (Symmetry 3.5 μm, 50 × 4.6 mm i.d) interfaced with a triple quadrupole tandem mass spectrometer. Positive electrospray ionization was employed as the ionization source. The mobile phase consisted of ammonium acetate (pH 7.8)-acetonitrile (10:90, v/v). The method was linear over a concentration range of 1–100 ngml−1. The lower limit of quantitation was 1 ngml−1. The intra-day and inter-day relative standard deviation across three validation runs over the entire concentration range was <11.5 %. The accuracy determined at three concentrations (8.0, 50.0 and 85.0 ngml−1 OLZ) was within ±1.21 % in terms of relative errors.

Kinetic and maximum-absorbance spectrophotometric methods for the determination of olanzapine

Two simple and sensitive spectrophotomet- ric methods were developed for the determination of olanzapine (OLZ) based on its oxidation with potassi- um iodate in a sulfuric acid medium to produce an intense violet-colored species exhibiting a maximum absorbance at 537 nm. The initial rate of formation and the maximum absorbance of the violet-colored oxidized product were monitored, in the first and sec- ond methods. The various experimental parameters affecting the rate of development and stability of the oxidized product were carefully studied and optimized. Beer 's law was obeyed up to 4.0 and 7.0 � gc m � 3 OLZ with correlation coefficients of 0.998 and 0.996 (n ¼ 6) and detection limits of 0.1 and 0.15 � gc m � 3 , for the initial rate and maximum absorbance methods. The proposed methods were conveniently applied to the determination of OLZ in its dosage forms and in spiked serum samples.

Isolation and characterization of process related impurities of olanzapine using HPLC and ESI‐MS/MS

An RP-HPLC method for the simultaneous separation and determination of olanzapine (OLZ) and its process impurities in bulk drugs and pharmaceutical formulations was developed. The separation was accomplished on Inertsil ODS 3V (4.6 mm x 250 mm; particle size 5 microm) column using 0.2 M ammonium acetate (pH = 4.50) and ACN as mobile phase in gradient elution mode. The analytes were monitored by a photo diode array (PDA) detector set at 254 nm and the flow rate was kept at 1.0 mL/min. The chromatographic behavior of all the compounds was examined under variable compositions of different solvents, buffer concentrations, and pH. The method was validated in terms of accuracy, precision, and linearity. Four unknown process impurities observed consistently during the analysis of different batches of OLZ were isolated and characterized by ESI-MS/MS, (1)H NMR, and FT-IR. The proposed RP-HPLC method was successfully applied to the analysis of commercial formulations. The method could be of use not only for rapid and routine evaluation of the quality of OLZ in bulk drug manufacturing units but also for the detection of its impurities in pharmaceutical formulations.

Highly sensitive spectrophotometric methods for the determination of olanzapine

Highly sensitive and selective spectrophotometric methods (A and B) were developed for the determination of micro amounts of olanzapine (OLZ). Method A (direct method) is based on the oxidation of olanzapine with a known excess of iodine monochloride (ICl) in an acidic medium. Under the same condition, thymol blue was iodinated by unreacted ICl, and the absorbance of uniodinated thymol blue was measured at 536 nm. The decrease in ICl concentration is a measure of drug concentration. In method B (indirect method), oxidation of OLZ by a known excess of Ce(IV) in sulfuric acid medium followed by the reaction of unreacted Ce(IV) with leuco crystal violet (LCV) to crystal violet (CV), which is measured in an acetate buffer medium ( pH 4.9) at 580 nm. These methods obey the Beer's law in the concentration range of 0.2-1.6 µg mL-1 (method A) and 0.1-1.4 µg mL-1 (method B). The developed procedures have been successfully applied to the determination of OLZ in pure and in dosage forms. The results exhibit no interference from the presence of excipients. The reliability of the methods was established by parallel determination of OLZ against the reference method.

Simultaneous Assay of Olanzapine and Fluoxetine in Tablets by Column High-Performance Liquid Chromatography and High-Performance Thin-Layer Chromatography

This paper describes validated high-performance liquid chromatographic (LC) and high-performance thin-layer chromatographic (TLC) methods for the simultaneous estimation of olanzapine and fluoxetine in pure powder and tablet formulations. The LC separation was achieved on a Lichrospher 100 RP-180, C18 column (250 mm, 4.0 mm id, 5 microm) using 0.05 M potassium dihydrogen phosphate buffer (pH 5.6 adjusted with o-phosphoric acid)-acetonitrile (50 + 50, v/v) as the mobile phase at a flow rate of 1 mL/min and ambient temperature. The TLC separation was achieved on aluminum sheets coated with silica gel 60F254 using methanol-toluene (40 + 20, v/v) as the mobile phase. Quantitation was achieved by measuring ultraviolet absorption at 233 nm over the concentration range of 10-70 and 40-280 microg/mL with mean recovery of 99.54 +/- 0.89 and 99.73 +/- 0.58% for olanzapine and fluoxetine, respectively, by the LC method. Quantitation was achieved by measuring ultraviolet absorption at 233 nm over the concentration range of 100-800 and 400-3200 ng/spot with mean recovery of 101.53 +/- 0.06 and 101.45 +/- 0.35% for olanzapine and fluoxetine, respectively, by the TLC method with densitometry. These methods are simple, precise, and sensitive, and they are applicable for simultaneous determination of olanzapine and fluoxetine in tablet formulations.

Determination of Olanzapine in rat brain using liquid chromatography with coulometric detection and a rapid solid-phase extraction procedure

A sensitive and selective method was developed for the determination of the antipsychotic drug Olanzapine levels in rat brain tissue, based on HPLC with electrochemical detection. The analyses were carried out on a C8 reversed phase column (150 mm × 4.6 mm, 5 μm), using a mobile phase composed of methanol and a phosphate buffer (44.0 mM, pH 3.5), containing triethylamine (21:79, v/v), flowing at 1.2 mL min −1. A high sensitivity coulometric detection analytical cell containing two flow-through low volume working electrodes was used: electrode 1 was set at +0.350 V and electrode 2 at −0.200 V. Olanzapine, administered to rats in different doses or in different times, was extracted from tissue homogenate of either the whole brain or specific areas (cortex, hyppocampus, nucleus striatum) with a rapid solid phase extraction procedure (SPE) on Oasis HLB cartridges. The method provided a high extraction yield of Olanzapine and internal standard (2-methylolanzapine) from brain tissue homogenate with absolute recovery values higher than 90.0%. The detector response was linear over a concentration range of 0.2–100.0 ng mL −1 of Olanzapine. The limit of quantification (LOQ) was 0.2 ng mL −1. Precision results, expressed by the intra-day and the inter-day relative standard deviation values, were satisfactory, better than 4.6%. Accuracy was satisfactory as well. This method proved to be suitable for the analysis of Olanzapine in rat brain tissues and for the study of distribution and pharmacokinetics of Olanzapine in rat brain after a single treatment with the antipsychotic drug.

Voltammetric, Spectrophotometric, and High Performance Liquid Chromatographic Analysis of Olanzapine

Three novel sensitive, simple, rapid, and precise methods namely voltammetric, spectrophotometric, and high performance liquid chromatographic have been developed for the quantitation of olanzapine in pharmaceutical dosage forms. Voltammetric studies cover three techniques; cyclic voltammetry (CV), differential pulse voltammetry (DPV), and osteryoung square wave voltammetry (OSWV). These techniques were used to investigate the electrooxidation of olanzapine. The data revealed that quantitative determination of this substance could be made by DPV and OSWV in the concentration range of 7.00 × 10−5 to 1.00 × 10−3 M. With CV technique the results were not satisfactory for quantitation. In the second method; the first derivative spectrophotometry was used and measurements of first derivative signals at 290.7 nm was taken. Linear calibration graph of first derivative values vs. concentration in the range 2.56 × 10−5 to 1.24 × 10−3 M were obtained with negligible intercepts. The third method, is based on high performance liquid chromatography (HPLC) on a reversed-phase column using a mobile phase of phosphate buffer pH: 5.5 and acetonitrile (7:3 v/v). The drug was monitored with a diode-array detector with a fixed wavelength 295.0 nm. Liquid chromatography was performed on a RP-YMC pack ODS A-132 C18 (5 µm, 15 cm × 6.0 mm) column. Linearity range for olanzapine was 1.61 × 10−6 to 7.24 × 10−4 M. All the proposed methods were successfully applied to the determination of olanzapine in pharmaceutical dosage forms with high percentage of recovery, good accuracy, and precision without any interference by the excipients.

Determination of olanzapine in human blood by liquid chromatography–tandem mass spectrometry

A liquid chromatographic–tandem mass spectrometric (LC–MS–MS) assay was developed and validated to quantitatively determine olanzapine (OLZ) concentrations in human blood. Liquid–liquid extraction, using n-butanol:cyclohexane (3:47, v/v), was used to isolate OLZ and its internal standard, LY170158, from the biological matrix. Chromatographic resolution of OLZ from endogenous interferences and known metabolites was accomplished with a MetaChem Monochrom HPLC column (4.6×150 mm, d p 5 μm). Detection occurred using a Perkin-Elmer Sciex API III Plus triple quadrupole mass spectrometer using positive ion APCI and multiple reaction monitoring (MRM). The linear dynamic range was from 5 to 500 ng ml −1 based on a 0.25-ml aliquot of human blood. The inter-day precision (%RSD) and accuracy (%RE) ranged from 3.65 to 10.64 and from −2.14 to 3.07, respectively. Modifications to an existing assay for the determination of OLZ in human plasma were necessary. A different structural analog was used as the internal standard due to instability observed for the original analog when using human blood as the matrix. A second modification was the addition of the anti-oxidant sodium ascorbate to inhibit degradation of OLZ in human blood, as has been noted by other investigators. Upon fortification of human blood with sodium ascorbate (final concentration, 0.33 m M), OLZ was found to be stable for at least 1 week at −70°C as well as through two freeze–thaw cycles. This assay, which will be used to investigate the distribution of OLZ in human blood, grants insight into the proper sample handling conditions needed to perform valid determinations of OLZ in human blood.

Determination of olanzapine and desmethylolanzapine in the plasma of schizophrenic patients by means of an improved HPLC method with amperometric detection

An improved HPLC method with electrochemical detection has been developed for the determination of olanzapine and its main metabolite, desmethylolanzapine, in human plasma. Chromatographic separation and analysis were performed on a C8 reversed-phase column with a mixture of methanol, acetonitrile, and pH 3.7 phosphate buffer as mobile phase; 2-methylolanzapine was used as internal standard. Careful pretreatment of the plasma samples was implemented by means of solid phase extraction (SPE).

Determination of olanzapine in human breast milk by high-performance liquid chromatography with electrochemical detection

A reversed-phase high-performance liquid chromatographic–electrochemical assay was developed and validated for the quantification of olanzapine in human breast milk. The assay involved a solid-phase extraction (SPE) of olanzapine and its internal standard on a Bond Elut Certify LRC mixed-mode cartridge. After conditioning of the SPE cartridge, human milk (1 ml) was passed through the cartridge. The cartridge was washed with five separate washing steps to remove endogenous compounds, and the analytes were eluted with ethyl acetate–ammonium hydroxide (98:2, v/v) solution. The eluate was evaporated to dryness (gentle stream of nitrogen at 40°C), and the residue was dissolved in mobile phase. The extract was injected onto a YMC basic column (150 mm×4.6 mm I.D., 5 μm particle size) at a flow-rate of 1 ml/min. A mixture of 75 m M phosphate buffer, pH 7.0–acetonitrile–methanol (48:26:26, v/v/v) was used as the mobile phase. Standard curves with a lower limit of quantitation of 0.25 ng/ml of olanzapine were linear ( r 2≥0.9992) over a range of 0.25–100 ng/ml. Based on the analysis of quality control (QC) samples, the average inter-day accuracy (RE) was 99.0% with an average precision (CV) of 6.64% over the entire range. The stability of olanzapine in human milk was established after three freeze–thaw–heat cycles and storage at −70°C for 10 months. The validated method was used to measure olanzapine concentrations in human milk during a clinical trial.

Determination of olanzapine in human plasma and serum by liquid chromatography/tandem mass spectrometry.

A liquid chromatographic/tandem mass spectrometric (LC/MS/MS) assay was developed for the quantitative determination of olanzapine (LY170053, OLZ) in human plasma and serum. Bond Elut C2 solid-phase extraction cartridges (single cartridge or 96-well format), in conjunction with a positive pressure manifold, were used to extract OLZ and its internal standard, LY170222, from the biological matrix. Chromatographic resolution of OLZ from endogenous plasma interferences and its metabolites was accomplished with a MetaChem monochrom HPLC (4.6 x 150 mm, dp 5 microns). Detection was effected with a Perkin-Elmer SCIEX API III Plus mass spectrometer using positive ion atmospheric pressure chemical ionization and a multiple reaction monitoring protocol. The linear dynamic range was from 250 pg ml-1 to 50 ng ml-1 of human plasma/serum using a 0.5 ml aliquot. The inter-day precision (relative standard deviation) and accuracy (relative error) in plasma ranged from 6.26 to 7.66% and from -3.54 to 7.52%, respectively. The intra-day precision and accuracy in serum ranged from 3.46 to 8.76% and from -8.06 to 12.46%, respectively. This assay is sensitive and selective, and will be used to support both human clinical and toxicological analyses. Furthermore, using the 96-well solid-phase extraction format, sample preparation can be easily automated.

Determination of olanzapine in human plasma and serum by liquid chromatography/tandem mass spectrometry

Determination of olanzapine in human plasma and serum by liquid chromatography/tandem mass spectrometry