Identification of 2-hydroxymethyl-olanzapine as a novel degradation product of olanzapine

Saar, Eva; Gerostamoulos, Dimitri; Drummer, Olaf H.; Beyer, Jochen

doi:10.1016/j.forsciint.2012.01.029

Cited by 12 publications

(7 citation statements)

References 29 publications

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“…Olanzapine is known to be unstable and susceptible to oxidation in biological matrices [31,32]. Levomepromazine, perazine, promazine, and promethazine are phenothiazines known to be easily oxidized to sulfoxides [33].…”

Section: Matrix Effects and Extraction Efficiencymentioning

confidence: 99%

Development and validation of a dynamic range-extended LC-MS/MS multi-analyte method for 11 different postmortem matrices for redistribution studies applying solvent calibration and additional 13C isotope monitoring

et al. 2015

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Postmortem redistribution (PMR) is one of numerous problems in postmortem toxicology making correct interpretation of measured drug concentrations difficult or even impossible. Time-dependent PMR in peripheral blood and especially in tissue samples is still under-explored. For further investigation, an easy applicable method for the simultaneous quantitation of over 80 forensically relevant compounds in 11 different postmortem matrices should be developed and validated overcoming the challenges of high inter-matrix and intra-matrix concentration variances. Biopsy samples (20 mg) or body fluids (20 μL) were spiked with an analyte mix and deuterated internal standards, extracted by liquid-liquid extraction, and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). For highest applicability, an easy solvent calibration was used. Furthermore, time-consuming dilution of high concentration samples showing detector saturation was circumvented by two overlapping calibration curves using (12)C isotope monitoring for low concentrations and (13)C isotopes for high concentration, respectively. The method was validated according to international guidelines with modifications. Matrix effects and extraction efficiency were strongly matrix and analyte dependent. In general, brain and adipose tissue produced the highest matrix effects, whereas cerebrospinal fluid showed the least matrix effects. Accuracy and precision results were rather matrix independent with some exceptions. Despite using an external solvent calibration, the accuracy requirements were fulfilled for 66 to 81 % of the 83 analytes. Depending on the matrix, 75-93 % of the analytes showed intra-day precisions at <20 %. (12)C and (13)C calibrations gave comparable results and proved to be a useful tool in expanding the dynamic range.

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Section: Matrix Effects and Extraction Efficiencymentioning

confidence: 99%

Development and validation of a dynamic range-extended LC-MS/MS multi-analyte method for 11 different postmortem matrices for redistribution studies applying solvent calibration and additional 13C isotope monitoring

et al. 2015

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“…Olanzapine failed to fulfil the validation criteria on both systems, even in higher concentrations. However, olanzapine is known to be unstable and problematic from the analytical point of view [40]. Possibly the use of the appropriate deuterated IS for olanzapine would have improved its accuracy and precision [41].…”

Section: Discussionmentioning

confidence: 99%

Comparison of conventional liquid chromatography–tandem mass spectrometry versus microflow liquid chromatography–tandem mass spectrometry within the framework of full method validation for simultaneous quantification of 40 antidepressants and neuroleptics in whole blood

Steuer

Poetzsch

Koenig

et al. 2015

Journal of Chromatography A

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“…OLP is recognised to display varying degrees of instability in both aqueous and biological matrices [22]. The extent of this instability is controversial, with contradictory reports on OLP behaviour in various environments [23,24,25].…”

Section: Methodsmentioning

confidence: 99%

Design and Development of Liquid Drug Reservoirs for Microneedle Delivery of Poorly Soluble Drug Molecules

et al. 2019

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The poor aqueous solubility of existing and emerging drugs is a major issue faced by the pharmaceutical industry. Water-miscible organic solvents, termed co-solvents, can be used to enhance the solubility of poorly soluble substances. Typically, drugs with poor aqueous solubility and Log P > 3 are not amenable to delivery across the skin. This study investigated the use of co-solvents as reservoirs to be used in combination with hydrogel-forming microneedles to enhance the transdermal delivery of hydrophobic compounds, namely Nile red, olanzapine and atorvastatin. A custom-made Franz cell apparatus was fabricated to test the suitability of a liquid drug reservoir in combination with polymeric microneedles. A co-solvency approach to reservoir formulation proved effective, with 83.30% ± 9.38% of Nile red dye, dissolved in 1 mL poly(ethylene glycol) (PEG 400), permeating neonatal porcine skin over 24 h. PEG 400 and propylene glycol were found to be suitable reservoir media for olanzapine and atorvastatin, with approximately 50% of each drug delivered after 24 h. This work provides crucial proof-of-concept evidence that the manipulation of microneedle reservoir properties is an effective method to facilitate microneedle-mediated delivery of hydrophobic compounds.

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Identification of 2-hydroxymethyl-olanzapine as a novel degradation product of olanzapine

Cited by 12 publications

References 29 publications

Development and validation of a dynamic range-extended LC-MS/MS multi-analyte method for 11 different postmortem matrices for redistribution studies applying solvent calibration and additional 13C isotope monitoring

Development and validation of a dynamic range-extended LC-MS/MS multi-analyte method for 11 different postmortem matrices for redistribution studies applying solvent calibration and additional 13C isotope monitoring

Comparison of conventional liquid chromatography–tandem mass spectrometry versus microflow liquid chromatography–tandem mass spectrometry within the framework of full method validation for simultaneous quantification of 40 antidepressants and neuroleptics in whole blood

Design and Development of Liquid Drug Reservoirs for Microneedle Delivery of Poorly Soluble Drug Molecules

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