Multidimensional Chromatographic Fingerprinting Combined with Chemometrics for the Identification of Regulated Plants in Suspicious Plant Food Supplements.

The popularity of plant food supplements has seen explosive growth all over the world, making them susceptible to adulteration and fraud. This necessitates a screening approach for the detection of regulated plants in plant food supplements, which are usually composed of complex plant mixtures, thus making the approach not so straightforward. This paper aims to tackle this problem by developing a multidimensional chromatographic fingerprinting method aided by chemometrics. To render more specificity to the chromatogram, a multidimensional fingerprint (absorbance × wavelength × retention time) was considered. This was achieved by selecting several wavelengths through a correlation analysis. The data were recorded using ultra-high-performance liquid chromatography (UHPLC) coupled with diode array detection (DAD). Chemometric modelling was performed by partial least squares-discriminant analysis (PLS-DA) through (a) binary modelling and (b) multiclass modelling. The correct classification rates (ccr%) by cross-validation, modelling, and external test set validation were satisfactory for both approaches, but upon further comparison, binary models were preferred. As a proof of concept, the models were applied to twelve samples for the detection of four regulated plants. Overall, it was revealed that the combination of multidimensional fingerprinting data with chemometrics was feasible for the identification of regulated plants in complex botanical matrices.

CBD oils on the Belgian market: A validated MRM GC-MS/MS method for routine quality control using QuEChERS sample clean up.

Quality control of CBD oils on the Belgium market showed that the CBD content not always corresponds to the label claim. There is a pressing need to develop new analytical methods specifically developed to the assay of such oily samples. Analytical issues are, however, encountered for routine analyses due to the matrix complexity, high cost of cannabinoid standards and low Δ9-THC concentrations. An oily matrix could cause technical damages to analytical instruments and reduce the lifetime of the chromatographic columns. This paper proposes a procedure combining a sample cleanup by QuEChERS, removing the oily matrix, followed by a validated MRM GC-MS/MS method for the routine analysis of CBD oil samples. Eighteen CBD samples were selected on the Belgium market for analysis. This method allows the quantification of CBD, the legality check for the Δ9-THC content by a CBN standard and the screening of seven other cannabinoids namely CBN, CBDV, CBT, CBC, Δ8-THC, THCV and CBG. The method was validated at three concentration levels (0.5-1-2% (w/v)) for CBD and (0.05-0.1-0.2% (w/v)) for CBN. The detection limits for CBT, CBD, CBC, Δ8-THC, CBN and for the other cannabinoids of interest, were 10 and 14 ng/mL respectively. The accuracy profile values for CBD and CBN showed that the ß-expectation tolerance intervals did not exceed the acceptance limits of ± 20%, meaning that 90% of future measurements will be included within this error range.

Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors.

BACKGROUND: Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD. METHODS: Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis RESULTS: No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II-IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis. CONCLUSION: These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.

Identification of (antioxidative) plants in herbal pharmaceutical preparations and dietary supplements.

The standard procedures for the identification, authentication, and quality control of medicinal plants and herbs are nowadays limited to pure herbal products. No guidelines or procedures, describing the detection or identification of a targeted plant or herb in pharmaceutical preparations or dietary supplements, can be found. In these products the targeted plant is often present together with other components of herbal or synthetic origin. This chapter describes a strategy for the fast development of a chromatographic fingerprint approach that allows the identification of a targeted plant in herbal preparations and dietary supplements. The strategy consists of a standard chromatographic gradient that is tested for the targeted plant with different extraction solvents and different mobile phases. From the results obtained, the optimal fingerprint is selected. Subsequently the samples are analyzed according to the selected methodological parameters, and the obtained fingerprints can be compared with the one obtained for the pure herbal product or a standard preparation. Calculation of the dissimilarity between these fingerprints will result in a probability of presence of the targeted plant. Optionally mass spectrometry can be used to improve specificity, to confirm identification, or to identify molecules with a potential medicinal or antioxidant activity.

Cost effectiveness of rituximab maintenance therapy in follicular lymphoma: long-term economic evaluation.

BACKGROUND: Rituximab maintenance therapy was shown to significantly extend overall survival (OS) and progression-free survival (PFS) in relapsed/refractory follicular lymphoma (FL) in the pivotal EORTC 20981 trial. OBJECTIVE: To assess the long-term costs and cost effectiveness of rituximab maintenance therapy after induction therapy versus current standard practice (observation) from the French National Health Service perspective. METHODS: A lifetime transition model was developed comparing rituximab maintenance with observation. PFS and OS were obtained from the EORTC 20981 trial with a median follow-up of 28 months and extrapolated from 2-year Kaplan-Meier curves using a Weibull distribution. PFS and OS benefits of rituximab were conservatively assumed to last only 5 years. Utility data were obtained from a multicentre observational study using the EQ-5D questionnaire. Direct medical costs were obtained from French official sources. All costs are reported in euro, year 2006 values. RESULTS: The EORTC 20981 study demonstrated that rituximab maintenance was effective in the management of relapsed/refractory FL. The model results showed that life expectancy and QALYs were increased by 22% and 28%, respectively, in patients treated with rituximab. The incremental cost-effectiveness ratios (ICERs) were euro 7612 per life-year gained and euro 8729 per QALY gained. In a one-way sensitivity analysis, most of the ICERs fell within the range of euro 7000-12,000. The results tend to show that rituximab maintenance therapy may be a cost-effective strategy in the management of relapsed/refractory FL in France, with ICERs below those observed for other therapies in the oncology field. The cost of rituximab was partly offset by the lower cost of relapse due to a longer time in the disease-free health state for patients in the rituximab arm.

Transdermal penetration behaviour of drugs: CART-clustering, QSPR and selection of model compounds.

A set of 116 structurally very diverse compounds, mainly drugs, was characterized by 1630 molecular descriptors. The biological property modelled in this study was the transdermal permeability coefficient logK(p). The main objective was to find a limited set of suitable model compounds for skin penetration studies. The classification and regression trees (CART) approach was applied and the resulting groups were discussed in terms of their role as possible model compounds and their determining descriptors. A second objective was to model transdermal penetration as a function of selected descriptors in quantitative structure-property relationships (QSPR) using a boosted CART (BRT) approach and multiple linear regression (MLR) analysis, where regression models were obtained by stepwise selection of the best descriptors. Evaluation of the standard statistical, as well as descriptor-number dependent, regression quality attributes yielded a maximal 10-dimensional MLR model. The CART and MLR models were subjected to an external validation with a test set of 12 compounds, not included in the original learning set of 104 compounds, to assess the predictive power of the models.