Ammonium acetate

The solvents were purchased in LC–MS grade from Carl Roth (Karlsruhe, Germany), Fisher Scientific (Schwer-te, Germany), or Sigma-Aldrich (Steinheim, Germany). Ammonium acetate was used from VWR (Darmstadt, Germany) and ammonia (25 vol%) was obtained from Grüssing (Filsum, Germany). Purified water was generated using a PureLab Flex2 system (Veolia Water Technologies, Celle, Germany). As internal standard for metabolic profiling d-(-)-α-phenylglycine was used, which was purchased from Sigma-Aldrich (Steinheim, Germany) in 99% purity. The concentrations, chemical structures and purities of the selected mycotoxins are defined in Online-Resource 1 (Figure S1, Table S1).

All reagents were of analytical purity. Allyl isothiocyanate and cysteamine were from Sigma-Aldrich (St. Louis, MO, USA). Congo red, bromocresol green and methyl red were from Reanal (Budapest, Hungary). Sinigrin was from Phytoplan (Heidelberg, Germany). Buffer components (disodium phosphate, ammonia, acetic acid, ammonium acetate) and ascorbic acid were from VWR (Debrecen, Hungary). As water, type I water (18.2 MΩ cm⁻¹) was used, which was produced by a Human Zeneer Power I water purification system (Human corporation, Seoul, Republic of Korea).

Methanol, 2-propanol, dichloromethane, water, ammonium-acetate were purchased from VWR International, LLC (Radnor, Radnor, PA, USA). All of them were of HPLC grade. Internal standard (ISTD) kits for quantitative lipidomic analysis of human samples were bought from AB Sciex Germany GmbH (Darmstadt, Germany). The kits contain ISTDs for 13 lipid classes including ceramides (Cers), cholesterolesters (CEs), DGs, acylceradmides (ACer), fatty acids (FAs), hexosylceramides (HexCers), lactosylceramides (LacCers), LPCs, LPEs, PCs, phosphatidylethanolamines (PEs), SMs, and TGs. The composition of ISTD standard mixtures containing isotope-labelled lipid molecules were described in detail previously [18 (link)]. Spike standards with quality control plasma kits, SelexION tuning kits, and system suitability test kits were also obtained from AB Sciex Germany GmbH.

Certified solution of 3-MeO-PCP, at 1 mg/mL in methanol, used to prepare the working solutions for the calibration curve was purchased from Sigma Aldrich (Saint-Quentin-Fallavier, France). MDMA-d5, used as internal standard, was obtained from Lipomed (Arlersheim, Switzerland) and diluted to appropriate concentrations. Ammonium formate, >99%, di-sodium tetraborate decahydrate and ammonium acetate were provided by VWR Chemicals (Leuven, Belgium). Formic acid for LC-MS was obtained from Carlo Erba (Chaussée du Vexin). HPLC-grade acetonitrile, methanol, dichloromet­hane, n-hexane, ethyl acetate and diethyl ether, acetic acid and 36% hydrochloric acid were obtained from VWR Prolabo (Fontenay-sous-Bois, France). Isoamyl alcohol, β-glucuronidase and heptafluorobutyric acid (HFBA) were purchased from Sigma Aldrich.

The model APIs for this study were RTV (Desano Pharmaceuticals, China) and LPV (Arene Life Sciences, India). The polymers for the preparation of the ASDs were either Kollidon® VA 64 fine (PVPVA, BASF, Germany) or the three different grades of AQOAT® LMP, MMP and HMP (HPMCAS, Shin Etsu, Japan). The film-coated tablet Kaletra® 200/50 mg was chosen as reference product. Fasted State Simulated Gastric Fluid (FaSSGF) and Fasted State Simulated Intestinal Fluid (FaSSIF) used as biorelevant dissolution media were prepared using ready-to-use powder mixtures (Biorelevant.com, United Kingdom). For each experiment, the media were freshly prepared according to the supplier manual. Decanol (Sigma Aldrich Chemie GmbH, Germany) was utilized as organic phase in the biphasic dissolution setup. Ammonium acetate, methanol HPLC grade and hydrochloric acid (all VWR Chemicals, Germany) were used for the preparation of the mobile phase for HPLC analysis. Polylactide (PLA) (Bavaria Filaments, Germany) was used as material for the additional 3D printed paddle for the biphasic dissolution studies.