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

Abstract

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.

Keywords: bioanalysis; instrumental analysis; olanzapine; sample preparation.

Figure 1

Structural formula of olanzapine.

Figure 2

Scheme of olanzapine metabolism in the liver.

Figure 3

Structural formulas of selected internal standards in the analysis of olanzapine.

Figure 4

Scheme of protein precipitation; olanzapine, matrix components, proteins.

Figure 5

Scheme of liquid–liquid extraction; olanzapine, matrix components.

Figure 6

Scheme of supported liquid extraction; olanzapine, matrix components, diatoms.

Figure 7

Scheme of solid-phase extraction; olanzapine, matrix components.

Figure 8

Scheme of micro extraction packed sorbent; olanzapine, matrix components.

Figure 9

Scheme of Dispersive Pipette XTRaction; olanzapine, matrix components, loose resin.

Figure 10

Scheme of Hybrid SPE–Precipitation; olanzapine, phospholipids, proteins.

Figure 11

Graphical diagrams of the column-switching system in the straight-flush and back-flush modes.

Figure 12

Retention mechanism in HILIC.

Figure 13

Proposed fragmentation of olanzapine by D. S. Patel [73].

Figure 14

Olanzapine degradation product in water samples proposed by the team of E. Saar [137].