Quetiapine

A human astrocyte cell line (C1028) was purchased from Shanghai Honsun Biological Technology Co., Ltd. (Shanghai, China). These astrocytes originated from the cortex of the human brain, and therefore should reflect the function of cortical astrocytes (He et al., 2020 (link)). Astrocytes were cultured in Dulbecco’s Modified Eagle Medium (DMEM) (Thermo Fisher Scientific, Wuhan, China) with 10% fetal bovine serum and 1% penicillin/streptomycin (Gibco Life Technologies, United States, A3160801 and 15140-122). The cells were cultured normally at 37°C with 5% CO₂ and saturated humidity. Antipsychotics including olanzapine (Sigma-Aldrich, St. Louis, MO, United States, PHR1825), quetiapine (Sigma-Aldrich, Q3638), risperidone (Sigma-Aldrich, R3030), and haloperidol (Sigma-Aldrich, H1512) were obtained commercially.

Ntera2 human teratocarcinoma cells (NT2) were cultured and differentiated as previously described.
⁹ (link) Following differentiation, the neuronal‐like cells (NT2‐N) were treated with the “BD drug cocktail” (2.5 mM lithium chloride, 0.5 mM valproate, 50 μM lamotrigine and 50 μM quetiapine; Sigma‐Aldrich, Castle Hill, Australia) or vehicle control (0.2% DMSO; Sigma‐Aldrich) for 24 h (n = 20 per group). Total RNA was extracted, quantified and quality controlled as previously described.
⁹ (link) RNAseq was performed as previously described.
⁹ (link)

Standard powders of quetiapine (Sigma-Aldrich, South Africa), olanzapine (Sigma-Aldrich, South Africa), fluconazole (Sigma-Aldrich, South Africa) and amphotericin B (Sigma-Aldrich, South Africa) were used in this study. quetiapine and olanzapine were prepared in dimethyl sulfoxide (Merck, South Africa) to each yield a stock solution of 1,000 mg/ml. fluconazole was reconstituted in distilled water (final stock solution of 1,000 mg/ml) while amphotericin B was dissolved in dimethyl sulfoxide (DMSO) (Merck, South Africa) to yield a stock concentration of 1,000 mg/ml. The concentrations of drug diluents, in which the stock solutions were prepared, never exceeded 1%.

Drug standards (cocaine, benzoylecgonine (BZE), heroin, 6‐acetylmorphine (6‐AM), cocaine‐d₃, benzoylecgonine‐d₃ (BZE‐d₃), heroin‐d₉ and 6‐acetylmorphine‐d₃ (6‐AM‐d₃)) were prepared from certified reference materials (Cerilliant, Round Rock, TX, USA) and were used to explore the extraction efficiency of paper spray mass spectrometry.
Certified reference materials of quetiapine, norquetiapine and quetiapine‐d₈ were obtained from Sigma Aldrich(St Louis, MO, USA) and were used to develop paper spray and LC/MS methods for the analysis of fingerprint samples.
Optima™ LC/MS grade methanol (MeOH), dichloromethane (DCM), acetonitrile (ACN), isopropanol (IPA) and water (H₂O) were used to prepare all solutions and solvent mixtures (Fisher Scientific, Madison, WI, USA). Formic acid or ammonium acetate (where applicable) was added to the mobile phase and spray solvents at 0.1% (v/v) or 10 mM (Fisher Scientific), respectively.

The main chemicals used in this study, including FGAs (chlorpromazine, chlorprothixene, clothiapine, droperidol, flupentixol, fluphenazine, haloperidol, levomepromazine, loxapine, pimozide, prochlorperazine, sulpiride, thioridazine, and trifluoperazine) and SGAs (amisulpride, aripiprazole, brexpiprazole, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, and zotepine) were acquired from Sigma-Aldrich (St. Louis, Missouri, USA) and were of highest purity grade. Before usage, the compounds were dissolved in dimethyl sulfoxide (DMSO) at the proper concentrations. Human hepatoma HepaRG™ cells were purchased from Thermo Fisher Scientific (Waltham, Massachusetts, USA). For 2 weeks, frozen cells were defrosted and kept alive in Williams’ E medium (Sigma-Aldrich, St. Louis, Missouri, USA) with 10% FetalClone™ II serum (HycloneTM, GE Healthcare, Chicago, Illinois, USA), 1 × L-glutamine, 5 μg/mL human insulin, and 50 μM hydrocortisone hemisuccinate without antibiotics as supplements. To produce differentiated hepatocyte-like features, the medium was then changed to the aforementioned medium plus 2% DMSO for an additional 2 weeks. Cells were grown at 37°C in a humidified 5% CO₂ environment. P-nitrophenylphosphate (PNPP) was used in an acid phosphatase (ACP) experiment to measure cell viability (29 (link)).

The following compounds were used: 7, 11, 16, imipramine (hydrochloride,
Adamed, Pienkow, Poland), escitalopram (hydrochloride; Adamed, Pienkow,
Poland), diazepam (Adamed, Pienkow, Poland), quetiapine (Adamed, Pienkow,
Poland), dizocilpine ((+)-MK-801, hydrogen maleate, Sigma-Aldrich,
U.K.). Compounds 7, 11, and 16 and quetiapine were suspended in a 1.5% solution of Tween 80 (Sigma-Aldrich,
U.K.), while diazepam, imipramine, escitalopram, and MK-801 were dissolved
in saline immediately before administration and injected intraperitoneally
(i.p.) at a volume of 2 mL/kg body mass. All of the compounds, with
the exception of imipramine and MK-801, which were injected 15 min
before the test, were administered 60 min before the tests. Control
animals received a vehicle (1.5% Tween 80 or saline) according to
the same injection regime.