Modifying wheat bran to improve its health benefits.

Consumption of wheat bran (WB) has been associated with improved gastrointestinal health and a reduced risk for colorectal cancer, cardiovascular diseases and metabolic disorders. These benefits are likely mediated by a combination of mechanisms, including colonic fermentation of the WB fiber, fecal bulking and the prevention of oxidative damage due to its antioxidant capacities. The relative importance of those mechanisms is not known and may differ for each health effect. WB has been modified by reducing particle size, heat treatment or modifying tissue composition to improve its technological properties and facilitate bread making processes. However, the impact of those modifications on human health has not been fully elucidated. Some modifications reinforce whereas others attenuate the health effects of coarse WB. This review summarizes available WB modifications, the mechanisms by which WB induces health benefits, the impact of WB modifications thereon and the available evidence for these effects from in vitro and in vivo studies.

Evaluation of impurities and dissolution profiles of illegal antimicrobial drugs encountered in Belgium.

Substandard and falsified (SF) antimicrobials are gaining popularity in both developing and developed countries, posing a growing threat to public health. In general, the evaluation of SF antimicrobial drugs mainly focuses on the identification and quantification of the pharmaceutical active ingredients, ignoring other parameters of drug quality control. This study performed an in-depth characterization and hazard identification of suspected SF antimicrobial medicinal products encountered in Belgium. In this comprehensive evaluation, impurity tests and dissolution studies were carried out. The dissolution profiles of illegal SF antimicrobials were mathematically compared to their genuine counterparts using the f1 and f2 -factor. The results indicated that 17 out of 57 illegal samples contained higher than permitted amounts of impurities and clearly demonstrated low equivalences of dissolution profiles between SF antimicrobials and genuine products. The variations between tablets at the different time points of the dissolution curves were also higher for the SF medicines. Moreover, 11 out of 19 illegal samples failed to meet the dissolution criteria prescribed by the United States Pharmacopeia. As impurities may induce adverse reactions and improper dissolution patterns may be the cause of insufficient drug efficacy, aggravation of illness and even promotion of antimicrobial resistance can be expected.

Spectroscopic techniques combined with chemometrics for fast on-site characterization of suspected illegal antimicrobials.

The threats of substandard and falsified (SF) antimicrobials, posed to public health, include serious adverse drug effects, treatment failures and even development of antimicrobial resistance. Next to these issues, it has no doubt that efficient methods for on-site screening are required to avoid that SF antimicrobials reach the patient or even infiltrate the legal supply chain. This study aims to develop a fast on-site screening method for SF antimicrobials using spectroscopic techniques (mid infrared, benchtop near infrared, portable near infrared and Raman spectroscopy) combined with chemometrics. 58 real-life illegal antimicrobials (claiming 18 different antimicrobials and one beta-lactamase inhibitor) confiscated by the Belgian Federal Agency for Medicines and Health Products (FAMHP) and 14 genuine antimicrobials were analyzed and used to build and validate models. Two types of models were developed and validated using supervised chemometric tools. One was used for the identification of the active pharmaceutical ingredients (APIs) by applying partial least squares-discriminant analysis (PLS-DA) and another one was used for the detection of non-compliant (overdosed or underdosed) samples by applying PLS-DA, k-nearest neighbors (k-NN) and soft independent modelling by class analogy (SIMCA). The best model capable of identifying amoxicillin and clavulanic acid (co-amoxiclav), azithromycin, co-trimoxazole and amoxicillin was based on the mid-infrared spectra with a correct classification rate (ccr) of 100%. The optimal model capable of detecting non-compliant samples within the combined group of amoxicillin and co-amoxiclav via SIMCA showed a ccr for the test set of 88% (7/8) using mid infrared or benchtop near infrared spectroscopy. The best model for detecting non-compliant samples within the group of amoxicillin via SIMCA was obtained using mid-infrared or Raman spectra, resulting in a ccr of 80% for the test set (4/5) and a ccr for calibration of 100%. For the group of co-amoxiclav, the optimal models showed a ccr of 100% for the detection of non-compliant samples by applying mid-infrared, benchtop near infrared or portable near infrared spectroscopy. Taken together, the obtained models, hyphenating spectroscopic techniques and chemometrics, enable to easily identify suspected SF antimicrobials and to differentiate non-compliant samples from compliant ones.

Development and validation of chromatographic methods for screening and subsequent quantification of suspected illegal antimicrobial drugs encountered on the Belgian market.

Estimations, made by the World Health Organization (WHO), state that 10% of the medical products in low- and middle-income countries are substandard or falsified (SF). Among them, antibiotics and antimalarials are the most commonly reported since 2013. Besides the fact that falsification is a crime, the worldwide use of poor quality antimicrobials could result in treatment failures, stronger antimicrobial resistance and even the promotion of the emergence of superbugs. Therefore, simple and accurate analytical methods are necessary, which are capable to detect and quantify a wide range of antimicrobials in suspected illegal products. In this work, a screening and a quantification method using ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS2) and diode array detection (UHPLC-DAD), respectively were developed and validated. These methods could be used for routine analysis and enable a more in-depth characterization of SF-antimicrobials. According to their popularity as SF-antimicrobials, 31 antibiotics, 3 antibacterial agents, 1 antifungal agent and 1 beta-lactamase inhibitor, covering eleven different antibacterial classes, were selected. The UHPLC-MS2 screening method with gradient elution is able to selectively detect these 36 compounds within 18 min (including wash and equilibration step). It was validated for sensitivity, selectivity and matrix effects. Within an analysis time of 32 min, the UHPLC-DAD method could quantify 32 compounds (4 showed insufficient UV absorbance) and resulted in sufficient selectivity, necessary since some SF-antimicrobials may include more than one antimicrobial component. This quantification method was validated for the positive hits found during screening tests of suspected illegal samples. This resulted in a validation set of 11 antimicrobials and 1 beta-lactamase inhibitor. The ''total error'' approach in accordance with the validation requirements of ISO-17025 was employed for the validation. 57 real-life illegal samples, seized by inspectors from the Belgium Federal Agency for Medicinal and Health Products (FAMHP), were analyzed using the two described methods. About half of them were not compliant and some samples that contained clavulanic acid showed a serious reduction in the amount of this molecule (in one sample only 14% of the claimed dosage was found). These quality issues might be attributed to either poor manufacturing, storage or transportation conditions.

Development and validation of LC methods for the separation of misoprostol related substances and diastereoisomers.

Misoprostol is a synthetic prostaglandin E1 analogue which is mainly used for prevention and treatment of gastric ulcers, but also for abortion due to its labour inducing effect. Misoprostol exists as a mixture of diastereoisomers (1:1) and has several related impurities owing to its instability at higher temperatures and moisture. A simple and robust reversed phase liquid chromatographic (RPLC) method is described for the separation of the related substances and a normal phase (NP) LC method for the separation of misoprostol diastereoisomers. The RPLC method was performed using an Ascentis Express C18 (150 mm × 4.6 mm, 5 µm) column kept at 35 °C. The mobile phase was a gradient mixture of mobile phase A (ACN-H2O-MeOH, 28:69:3 v/v/v) and mobile phase B (ACN-H2O-MeOH, 47:50:3 v/v/v) eluted at a flow rate of 1.5 mL/min. UV detection was performed at 200 nm. The NPLC method was undertaken by using an XBridge bare silica (150 mm × 2.1 mm, 3.5 µm) column at 35 °C. The mobile phase contained 1-propanol-heptane-TFA (4:96:0.1%, v/v/v), pumped at a flow rate of 0.5 mL/min. UV detection was performed at 205 nm. This LC method can properly separate the two diastereoisomers (Rs > 2) within an analysis time of less than 20 min. Both methods were validated according to the ICH guidelines. Furthermore, these new LC methods have been successfully applied for purity control and diastereoisomers ratio determination of misoprostol bulk drug, tablets and dispersion.