A simple and automated online SPE-LC-MS/MS method for simultaneous determination of olanzapine, fluoxetine and norfluoxetine in human plasma and its application in therapeutic drug monitoring

Abstract

The olanzapine-fluoxetine augmentation strategy has been proved efficacious for treatment-resistant depression, psychotic depression and bipolar depression. To achieve efficient therapeutic drug monitoring (TDM), we develop an automated online SPE-LC-MS/MS method for the simultaneous quantification of olanzapine, fluoxetine and norfluoxetine in human plasma. After adding an internal standard of diphenhydramine and centrifugation, a 10 mL plasma sample was directly injected into the SPE cartridge. While the analytes were retained on the SPE cartridge, the endogenous materials were washed out by the loading solvent. Following the valve switching, the analytes were eluted from the SPE cartridge to the analytical column by gradient elution. The analytes were quantified using a triplequadrupole tandem mass spectrometer. Calibration curves were linear over the concentration range of 0.25-50.00 ng mL À1 for olanzapine, and 0.50-100.00 ng mL À1 for fluoxetine and norfluoxetine. The intra-and inter-day precisions were within 1.17% and 4.63%. And the accuracies were between 95.60% and 101.48%. The mean matrix effect was in the range of 90.35% to 99.89% and mean recovery was in the range of 90.35% to 96.99%. This method has been successfully applied to two Chinese schizophrenia patients. The online SPE-LC-MS/MS method allows sensitive and robust quantification of olanzapine, fluoxetine and norfluoxetine for routine TDM in clinic.

A review of the modern principles and applications of solid-phase extraction techniques in chromatographic analysis

“…The mixed functional phase (MFP) consists of both hydrophilic polyoxyethylene and hydrophobic styrene groups embedded in a siloxane polymer coating on a porous silica particle (8 nm) was prepared. As a result, only the hydrophilic, non-adsorption polymer network interacts with matrix components, allowing them to elute within the void volume [ 51 ]. Several commercial mixed extraction materials are available with phenyl and C 8 as hydrophobic moieties or functionalized strong CX groups instead of styrene groups.…”

Recent advances in liquid chromatographic methods for the determination of selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors

“…Extraction recovery was modest (~60%), suggesting the possibility of improvement. Fan et al () developed an online SPE‐LC–MS/MS method with an LOQ of 0.5 ng/ml. An automated six‐port switching valve shortened sample preparation time and enabled both cartridge cleaning during chromatographic separation and column conditioning during SPE elution.…”

Development of a validated liquid chromatography–diode array detection method for simultaneous determination of olanzapine and fluoxetine in their combined formulation: Application to greenness assessment

“…FLN is chemically (±)-N-methyl-3-phenyl-3-(α,α,α-trifluoro-ptolyloxy)propylamine hydrochloride (Figure S1B) is used as an antidepressant [15]. In their combined dosage form, OLN and FLN are indicated to treat bipolar psychosis [16].OLN and FLN are simultaneously assayed by many liquid chromatographic techniques such as UV spectrophotometry [17,18,21], HPTLC [19][20][21], HPLC [19,[21][22][23][24][25][26][27][28][29], and LC-MS [30][31][32][33][34][35]. However, several drawbacks such as lower sensitive linear dynamic range, complex mobile phase composition employing multiple organic phases and peak modifiers, possible precipitation of mobile phase due to use of ammonium buffer with acetonitrile and methanol, higher flow rates, lack of robustness information, and longer run times were found with the existing HPLC methods (Table S1).…”