Editorial: Advances in therapeutic drug monitoring of psychiatric subjects: Analytical strategies and clinical approaches

Despite the long and sometimes enthusing history of pharmacological therapy in psychiatry, the hard truth is that unfortunately a quite large percentage of patients is still not responding, or poorly responding, to treatment, leading to many life years lost to disability, many lost lives, and an immeasurable amount of suffering from patients, relatives, friends, and caregivers alike. Thus, any scientific advance and any practice that could lead to even a slight increase in psychiatric therapy effectiveness would also bring with them enormous benefits for both citizens and healthcare institutions. It is a strong conviction, after many years of practice and study, that therapeutic drug monitoring (TDM) is one of these practices, one that is continually advancing and progressing both from the analytical and clinical points of view, toward the final goal of better, personalized, precision medicine

Threat or treat: Exposure assessment and risk characterisation of chemical contaminants in soft drinks and chocolate bars in various Polish population age groups

In the frame of the European Food Risk Assessment (EU-FORA) fellowship programme, two studies on chemical contaminants in food matrices were carried out in Warsaw, Poland, at the Department of Food Safety and Chemical Analysis, Institute of Agricultural and Food Biotechnology. The first study addressed health concerns about the dietary exposure to bisphenol A (BPA) contamination due to consumption of soft drink by Polish population. BPA is an organic additive used in the production of epoxy resins and polycarbonate plastics and because of this it is used in the internal coating of cans and in plastic bottle production. Depending on several factors, BPA can migrate from these materials to the soft drink and so, it can be ingested by consumers causing hormonal and reproductive disorders. To estimate the Polish population exposure to BPA, several soft drinks belonging to different brands were purchased from a supermarket in the city of Warsaw and analysed. The result of the analysis highlight that mean BPA exposure in the Polish population exceeds the tolerable daily intake proposed by the EFSA scientific opinion, raising health concerns. On the other hand, the second study, focused on cadmium exposure due to chocolate consumption by Polish population, did not raise any health concern. Cadmium is a heavy metal that naturally occurs in its inorganic form in the environment and its presence in chocolate derives only from the cocoa beans and not from contamination during processing. Its accumulation in the human body can create several adverse effects, including renal dysfunction and failure. To estimate the Polish population exposure to cadmium, several chocolate bars were purchased from a supermarket in the city of Warsaw and analysed. The results of the analysis show that cadmium exposure in the Polish population does not exceed the tolerable weekly intake proposed by the EFSA scientific opinion

Evaluation of the Antioxidant Capacity of Fruit Juices by Two Original Analytical Methods

Two analytical methods previously developed by our groups were employed to estimate the antioxidant capacity of commercial fruit juices. The electrochemical method, which measures the scavenging activity of antioxidants towards OH radicals generated by both hydrogen peroxide photolysis and Fenton’s reaction, is based on the recovery of the cyclic voltametric response of the redox probe Ru(NH3)63+ at a Glassy Carbon electrode modified with a thin film of an insulating polyphenol, in the presence of compounds with antioxidant properties. The values of the antioxidant capacity of the fruit juices are expressed as vitamin C equivalents/L. The chromatographic method is based on the generation of OH radicals via Fenton’s reaction in order to test the inhibition of their formation in the presence of antioxidant compounds by monitoring salicylate aromatic hydroxylation derivatives as markers of •OH production, by means of HPLC coupled to coulometric detection. The results are expressed as the percentage of inhibition of •OH production in the presence of the tested juice compared to the control sample. When OH radicals are produced by Fenton’s reaction, the antioxidant capacity of the juices, estimated by both methods, displays an analogous trend, confirming that they can be considered an alternative for measuring the ability of antioxidants to block OH radical formation

Assessment of capillary volumetric blood microsampling for the analysis of central nervous system drugs and metabolites

Therapeutic drug monitoring (TDM) is an important tool for correlating the administered drug dose to drug and metabolite concentrations in the body and to therapeutic and adverse effects. In the case of treatment with drugs active on the central nervous system (CNS), frequent TDM becomes really useful, especially for patient compliance checking and for therapy optimisation. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline, chosen as target compounds for this study, are two antidepressants mainly used for major depression, but also for obsessive-compulsive disorder associated with neurodegenerative diseases and for eating disorders. Microsampling approaches can be used to make TDM patient-friendly, by means of minimally invasive fingerpricking instead of classic invasive venipuncture. In this study, an innovative volumetric microsampling approach based on the use of hemaPEN technology is proposed to simultaneously obtain four identical dried whole blood microsamples by means of a single capillary sampling. The developed strategy shows significant advantages in terms of blood collection and storage, fast and feasible extraction procedure and sensitive LC-MS/MS analysis, also providing satisfactory validation results (extraction yield >81%, RSD <12.0%, and <6.3% loss in analyte stability after 3 months). The proposed methodology has proven to be sound and reliable for application to the TDM of psychiatric patients treated with antidepressant drugs such as fluoxetine and sertraline. The original capillary volumetric microsampling procedure using hemaPEN has been demonstrated to be suitable for the accurate sampling of capillary whole blood, in order to be successfully exploited in self- and home-sampling procedures in future and to pave the way for precision medicine approaches for the treatment of CNS disorders

Volumetric Absorptive Microsampling (VAMS) for Targeted LC-MS/MS Determination of Tryptophan-Related Biomarkers

L-Tryptophan (TRP) metabolites and related biomarkers play crucial roles in physiological functions, and their imbalances are implicated in central nervous system pathologies and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, schizophrenia and depression. The measurement of TRP metabolites and related biomarkers possesses great potential to elucidate the disease mechanisms, aid preclinical drug development, highlight potential therapeutic targets and evaluate the outcomes of therapeutic interventions. An effective, straightforward, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of 24 TRP-related compounds in miniaturised murine whole blood samples. Sampling and sample pretreatment miniaturisation were achieved thanks to the development of a volumetric dried blood microsampling approach. Volumetric absorptive microsampling (VAMS) allows the accurate sampling of microvolumes of blood with advantages including, but not limited to, minimal sampling invasiveness, logistical improvements, method sustainability in terms of solvents and energy consumption, and improvement of animal studies in the framework of the 3Rs (Replacement, Reduction and Refinement) principles on animal welfare. The VAMS-LC-MS/MS method exhibited good selectivity, and correlation coefficient values for the calibration curves of each analyte were >0.9987. The limits of quantitation ranged from 0.1 to 25 ng/mL. The intra- and inter-day precisions in terms of RSD were <9.6%. All analytes were stable in whole blood VAMS samples stored at room temperature for at least 30 days with analyte losses < 14%. The developed method was successfully applied to the analysis of biological samples from mice, leading to the unambiguous determination of all the considered target analytes. This method can therefore be applied to analyse TRP metabolites and related biomarkers levels to monitor disease states, perform mechanistic studies and investigate the outcomes of therapeutic interventions

Enhanced urinary stability of peptide hormones and growth factors by dried urine microsampling

Volumetric absorptive microsampling (VAMS) and dried urine spot (DUS) strategies were applied for the collection of dried microsamples for anti-doping testing of low-stability peptide hormones and growth factors prohibited by the World Anti-Doping Agency (WADA). Drying, storage and transport conditions, as well as pretreatment steps, were optimised before liquid chromatography - tandem mass spectrometry (LC–MS/MS) analysis. The analytical method has been fully validated in terms of sensitivity (limits of quantitation 0.3−10 ng/mL), precision (RSD% < 6.6 %) and extraction yields (78–91 %). Dried microsample stability studies (90 days) have been performed and compared to fluid urine stability. Significantly higher losses have been observed in fluid urine stored at −20 °C (up to 55 %) and −80 °C (up to 29 %) than in dried urine microsamples stored at room temperature (< 19 %). The final microsampling and analysis protocols allow the collection of urine microvolumes, unlikely to be tampered, stably storable and shippable with no particular precautions for possible anti-doping testing of prohibited peptides and hormones

Botanical sources, chemistry, analysis, and biological activity of furanocoumarins of pharmaceutical interest

The aim of this work is to provide a critical review of plant furanocoumarins from different points of view, including their chemistry and biosynthetic pathways to their extraction, analysis, and synthesis, to the main biological activities found for these active compounds, in order to highlight their potential within pharmaceutical science. The limits and the possible improvements needed for research involving these molecules are also highlighted and discussed

Vitamin c—sources, physiological role, kinetics, deficiency, use, toxicity, and determination

Vitamin C (L‐ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facili-tation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro‐oxidant than an anti‐oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins. The role of vitamin C is well demonstrated by miscellaneous symptoms of its absence—scurvy. The only clini-cally well‐documented indication for vitamin C is scurvy. The effects of vitamin C administration on cancer, cardiovascular diseases, and infections are rather minor or even debatable in the general population. Vitamin C is relatively safe, but caution should be given to the administration of high doses, which can cause overt side effects in some susceptible patients (e.g., oxalate renal stones). Lastly, analytical methods for its determination with advantages and pitfalls are also discussed in this review

Oral D-Aspartate Treatment Improves Sperm Fertility in Both Young and Adult B6N Mice

D-Aspartate (D-Asp) treatment improved the fertility of young male C57BL/6N mice in vivo revealing a direct role on capacitation, acrosome reaction, and fertility in vitro in young males only. We investigated whether the positive effect of D-Asp on fertility could be extended to adult males and evaluated the efficacy of a 2- or 4-week-treatment in vivo. Therefore, 20 mM sodium D-Asp was supplied in drinking water to males of different ages so that they were 9 or 16 weeks old at the end of the experiments. After sperm freezing, the in vitro fertilization (IVF) rate, the birth rate, hormone levels (luteinizing hormone (LH), epitestosterone, and testosterone), the sperm quality (morphology, abnormalities, motility, and velocity), the capacitation rate, and the acrosome reaction were investigated. Oral D-Asp treatment improves the fertilizing capability in mice regardless of the age of the animals. Importantly, a short D-Asp treatment of 2 weeks in young males elevates sperm parameters to the levels of untreated adult animals. In vivo, D-Asp treatment highly improves sperm quality but not sperm concentration. Therefore, D-Asp plays a beneficial role in mouse male fertility and may be highly relevant for cryorepositories to improve mouse sperm biobanking

Improved achiral and chiral hplc-uv analysis of ruxolitinib in two different drug formulations

In this paper, two new reversed-phase (RP) HPLC-UV methods enabling the quantitative achiral and chiral analysis of ruxolitinib in commercial tablets (containing 20 mg of active pharmaceutical ingredient, API) and not commercially available galenic capsules (with 5 mg of API) are described. For the achiral method based on the use of a water/acetonitrile [70:30, v/v; with 0.1% (v) formic acid] eluent, a “research validation” study was performed mostly following the “International Council for Harmonization” guidelines. All the system suitability parameters were within the acceptance criteria: tailing factor, between 1.7 and 2.0; retention factor, 2.2; number of theoretical plates, >9000. The linearity curve showed R2 = 0.99 (Rxv2 = 0.99), while trueness (expressed as recovery) was between 96.3 and 106.3%. Coefficient of variations (CVs) (repeatability: CVw and intermediate precision: CVIP ) did not exceed 1.3% and 2.9%, respectively. Moreover, the use of the enantiomeric Whelk-O1 chiral stationary phases operated under similar RP eluent conditions as for the achiral analyses, and the “inverted chirality columns approach (ICCA)” allowed us to establish that the enantiomeric purity of ruxolitinib is retained upon reformulation from tablets to capsules. The two developed methods can allow accurate determinations of ruxolitinib in drug formulations for medical use