As a prescription drug, retinoic acid is listed as a banned cosmetic additive in the EU and China regulations. Currently, spectrophotometric methods, including thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and HPLC–MS/MS, are commonly used for the determination of retinoic acid. As these conventional methods require complex pretreatment and are time-consuming, chemical derivatization combined with paper spray ionization mass spectrometry was developed for the fast detection of retinoic acid in cosmetics. N,N-dimethylpiperazine iodide (DMPI) was utilized as a derivatization reagent. Carboxylic acid in retinoic acid was derivatized to carry a positive charge and was subjected to mass spectrometry analysis. Results showed that compared with non-derivatized compounds, the detection limit was increased by about 50 times. The linearity in the range of 0.005–1 μg·mL⁻¹ was good. The limit of detection (LOD) was 0.0013 μg·mL⁻¹, and the limit of quantification (LOQ) was 0.0043 μg·mL⁻¹. The recoveries of spiked samples were in the range of 95–105%, and the RSDs were below 5%. Derivatization and paper spray ionization MS render a quick, sensitive, and accurate method for the detection of retinoic acid in a complex matrix.

Chromatography–mass spectrometry typically requires a time-consuming and costly pretreatment to detect illegal additives in cosmetics. Retinoic acid is classified as a prohibited additive in cosmetics by the European Union and China. Therefore, a rapid and convenient method is needed for its detection. In this study, a method for detecting retinoic acid using Reactive Paper Spray Ionization Mass Spectrometry was developed. N′-dimethylpiperazine was used as the derivatization reagent due to its ability to react with carboxyl functional groups at room temperature. Our results indicate that the derivatized retinoic acid compounds obtained using this method exhibited good linearity within the range of 0.0005~0.1 μg·mL⁻¹, achieving a limit of detection of 0.107 ng·mL⁻¹.

Oral delivery of semaglutide offers a promising strategy for type 2 diabetes mellitus (T2DM) by improving patient adherence. However, its clinical translation is limited by low oral bioavailability, resulting from the peptide’s hydrophilicity, instability in gastrointestinal environments, and poor intestinal permeability. To address these challenges, semaglutide was converted into a hydrophobic ion-pair (HIP) complex with the cationic lipid DODAB (termed SEDAB), which was subsequently incorporated into a self-microemulsifying drug delivery system (SMEDDS), yielding SEDAB-SME. A comparative screen of two cationic amphiphiles identified DODAB as the selected counterion, which forms a stable complex with semaglutide. Ion pairing with DODAB markedly increased the lipophilicity of semaglutide, and the resulting SEDAB-SME formulation enhanced its stability in simulated intestinal fluid, effectively protecting the peptide from enzymatic degradation. In vitro, FITC-semaglutide delivered by SEDAB-SME showed markedly greater cell association than native FITC-semaglutide, and inhibitor studies suggested the involvement of a cholesterol-sensitive, raft-associated internalization route. In an intra-jejunal (i.j.) regional intestinal absorption study in SD rats, SEDAB-SME enhanced jejunal absorption of semaglutide (Frel = 0.12%) by approximately 28-fold compared with native semaglutide administered via the same i.j. route. In an acute single-dose pharmacodynamic study in STZ-induced T2DM rats, oral administration of SEDAB-SME enteric-coated capsules significantly reduced blood glucose levels. These results demonstrate that the HIP-SMEDDS strategy markedly enhanced regional jejunal absorption and produced acute glucose-lowering effects in a rodent model. This proof-of-concept study highlights a promising approach that warrants further validation of direct oral pharmacokinetics and long-term safety.