Concurrent supercritical fluid chromatographic analysis of terpene lactones and ginkgolic acids in Ginkgo biloba extracts and dietary supplements.

Supercritical fluid chromatography was used to resolve and determine ginkgolic acids (GAs) and terpene lactones concurrently in ginkgo plant materials and commercial dietary supplements. Analysis of GAs (C13:0, C15:0, C15:1, and C17:1) was carried out by ESI (-) mass detection. The ESI (-) spectra of GAs simply displayed only the [M-H](-) pseudo-molecular ions, and selected ion monitoring (SIM) for those ions was used for the quantification. Analysis of terpene lactones (ginkgolides A, B, C, J and bilobalide) was complicated by in-source collision-induced dissociation (IS-CID) in the ESI source. Thus, MS analysis could be influenced by the fragmentation pattern produced by the IS-CID. However, it was established that the fragmentation pattern, measured by ion survival yield (ISY), was independent of analyte concentration or matrix at a fixed cone voltage in the ESI source. Therefore, MS with SIM mode was applicable for the analysis of these analytes. The reported method provided consistent and sensitive analysis for the analytes of interest. The LOQs and LODs were determined to be below 100 and 40 ng/mL for GAs and 1 µg/mL and 400 ng/mL for terpene lactones, respectively. Intra- and inter-day precisions were found to be satisfactory with RSDs being below 5.2 %. Analyte recoveries ranged from 87 to 109 %. The developed method was successfully applied to the analysis of 11 ginkgo plant samples and 8 dietary supplements with an analysis time of less than 12 min.

Sodium thiosulfate for the treatment of warfarin-induced calciphylaxis in a nondialysis patient.

Calciphylaxis or uremic arteriolopathy is a complex process typically seen in patients with end-stage renal disease, but has also been reported in patients with normal renal function. However, therapies for calciphylaxis are based on reports of traditional patients (i.e., end-stage renal disease). A mainstay of therapy, sodium thiosulfate (STS), has been shown to be effective for the treatment of calciphylaxis. Without a standardized therapy reported for nondialysis patients there is a need for evidence-based therapy. Here, we report a case of a 63-year-old woman with an acute injury on chronic kidney disease (CrClBaseline = 48 mL/min, CrClAKI = 36 mL/min), not requiring dialysis, with warfarin-induced calciphylaxis. After 4 weeks of therapy with STS, sevelamer, alendronate, and enzymatic debridement the patient subjectively reported slight improvement of the necrotic ulcers but developed cellulitis on her nonaffected limb. Additionally, after 12 weeks of therapy she was readmitted for renal failure and subsequently required dialysis.

Comparison of three chromatographic techniques for the detection of mitragynine and other indole and oxindole alkaloids in Mitragyna speciosa (kratom) plants.

Leaves of the Southeast Asian plant Mitragyna speciosa are used to suppress pain and mitigate opioid withdrawal syndromes. The potential threat of abuse and ready availability of this uncontrolled psychoactive plant have led to the need for improved analytical techniques for the detection of the major active components, mitragynine and 7-hydroxymitragynine. Three independent chromatographic methods coupled to two detection systems, GC with MS, supercritical fluid chromatography with diode array detection, and HPLC with MS and diode array detection, were compared for the analysis of mitragynine and other indole and oxindole alkaloids in M. speciosa plants. The indole alkaloids included two sets of diastereoisomers: (i) paynantheine and 3-isopaynantheine and (ii) mitragynine, speciogynine, and speciociliatine. Two oxindole alkaloid diastereoisomers, corynoxine and corynoxine B, were also studied. The HPLC and supercritical fluid chromatography methods successfully resolved the major components with slightly different elution orders. The GC method was less satisfactory because it was unable to resolve mitragynine and speciociliatine. This separation was difficult by GC with a liquid stationary phase because these diastereoisomers differ only in the orientation of an interior hydrogen atom. The observed lack of resolution of the indole alkaloid diastereoisomers coupled with the likeness of the mass and tandem mass spectra, calls into question proposed GC methods for the analysis of mitragynine based on solely GC with MS separation and identification.

Basis set dependence of higher-order correlation effects in π-type interactions.

The basis set dependence of higher-order correlation effects on π-type interaction energies was examined by scanning the potential energy surfaces of five dimer systems. The dimers of acetylene (H-C≡C-H), diacetylene (H-C≡C-C≡C-H), cyanogen (N≡C-C≡N), diphosphorous (P≡P), and 1,4-diphosphabutadiyne (P≡C-C≡P) were studied in three different configurations: cross, parallel-displaced, and t-shaped. More than 800 potential energy curves (PECs) were generated by computing the interaction energies for all 15 dimer configurations over a range of intermolecular distances with the MP2, coupled-cluster single double (CCSD), and coupled-cluster single double triple (CCSD(T)) methods in conjunction with 21 basis sets ranging from a small 6-31G*(0.25) split-valence basis set to a large aug-cc-pVQZ correlation consistent basis set. Standard extrapolation techniques were also used to construct MP2, CCSD, and CCSD(T) complete basis set (CBS) limit PECs as well as CBS limit higher-order correlation corrections based on the differences between CCSD(T) and MP2 interaction energies, denoted δ(MP2)(CCSD(T)), and the corresponding differences between CCSD(T) and CCSD interactions energies, denoted δ(CCSD)(CCSD(T)). Double-ζ basis sets struggled to reproduce the former but provided quite reasonable descriptions of the latter as long as diffuse functions were included. The aug-cc-pVDZ basis deviated from the δ(CCSD)(CCSD(T)) CBS limit by only 0.06 kcal mol(-1) on average and never by more than 0.24 kcal mol(-1), whereas the corresponding deviations were approximately twice that for the δ(MP2)(CCSD(T)) term. While triple-ζ basis sets typically improved results, only aug-cc-pVTZ provided appreciable improvement over utilizing the aug-cc-pVDZ basis set to compute δ(CCSD)(CCSD(T)). Counterpoise (CP) corrections were also applied to all double- and triple-ζ basis sets, but they rarely yielded a better description of these higher-order correlation effects. CP corrections only consistently improved results when the aug-cc-pVDZ basis set was used to compute δ(MP2)(CCSD(T)), yielding mean and maximum absolute deviations from the CBS values of 0.10 and 0.39 kcal mol(-1), respectively, for all five dimer systems.

Accurate Interaction Energies for Problematic Dispersion-Bound Complexes: Homogeneous Dimers of NCCN, P2, and PCCP.

All intermolecular interactions involve London dispersion forces. The accurate treatment of dispersion is essential for the computation of realistic interaction potentials. In general, the most reliable method for computing intermolecular interactions is coupled-cluster singles and doubles with perturbative triples [CCSD(T)] in conjunction with a sufficiently flexible Gaussian atomic orbital basis set, a combination which is not routinely applicable due to its excessive computational demands (CPU time, memory, storage). Recently, many theoretical methods have been developed that attempt to account for dispersion in a more efficient manner. It is well-known that dispersion interactions are more difficult to compute in some systems than others; for example, π-π dispersion is notoriously difficult, while alkane-alkane dispersion is relatively simple to compute. In this work, numerous theoretical methods are tested for their ability to compute reliable interaction energies in particularly challenging systems, namely, the P2, PCCP, and NCCN dimers. Symmetry-adapted perturbation theory (SAPT) is applied to these dimers to demonstrate their sensitivity to the treatment of dispersion. Due to the small size of these systems, highly accurate CCSD(T) potential energy curves could be estimated at the complete basis set limit. Numerous theoretical methods are tested against the reliable CCSD(T) benchmarks. Methods using a treatment of dispersion that relies on time-dependent density functional theory (TDDFT) response functions are found to be the most reliable.

Glycemic responses to sweetened dried and raw cranberries in humans with type 2 diabetes.

This study assessed the metabolic response to sweetened dried cranberries (SDC), raw cranberries (RC), and white bread (WB) in humans with type 2 diabetes. Development of palatable cranberry preparations associated with lower glycemic responses may be useful for improving fruit consumption and glycemic control among those with diabetes. In this trial, type 2 diabetics (n= 13) received WB (57 g, 160 cal, 1 g fiber), RC (55 g, 21 cal, 1 g fiber), SDC (40 g, 138 cal, 2.1 g fiber), and SDC containing less sugar (SDC-LS, 40 g, 113 cal, 1.8 g fiber + 10 g polydextrose). Plasma glucose (mmol/L) peaked significantly at 60 min for WB, and at 30 min for RC, SDC, and SDC-LS at 9.6 ± 0.4, 7.0 ± 0.4, 9.6 ± 0.5, and 8.7 ± 0.5, respectively, WB remained significantly elevated from the other treatments at 120 min. Plasma insulin (pmol/mL) peaked at 60 min for WB and SDC and at 30 min for RC and SDC-LS at 157 ± 15, 142 ± 27, 61 ± 8, and 97 ± 11, respectively. Plasma insulin for SDC-LS was significantly lower at 60 min than either WB or SDC. Insulin area under the curve (AUC) values for RC and SDC-LS were both significantly lower than WB or SDC. Phenolic content of SDC and SDC-LS was determined following extraction with 80% acetone prior to high-performance liquid chromatography (HPLC) and electronspray ionization-mass spectrometry (ESI-MS) and found to be rich in 5-caffeoylquinic cid, quercetin-3-galactoside, and quercetin-3-galactoside, and the proanthocyanidin dimer epicatechin. In conclusion, SDC-LS was associated with a favorable glycemic and insulinemic response in type 2 diabetics. Practical Application: This study compares phenolic content and glycemic responses among different cranberry products. The study seeks to expand the palatable and portable healthy food choices for persons with type 2 diabetes. The novel use of polydextrose as a bulking agent making possible a reduction in caloric content and potential glycemic response is also characterized in this study.