Dezhi Yang

Salt screening and characterization of ciprofloxacin.

With the aim of improving the solubility of ciprofloxacin, polybasic organic acids were utilized to react with ciprofloxacin in different stoichiometric proportions. The use of the solvent drop grinding (SDG) method, as well as the solvent evaporation method, resulted in the crystalline salts ciprofloxacin/fumaric acid (1:1, 2:1), ciprofloxacin/maleic acid (1:1) and ciprofloxacin/citric acid (2:1). The solubilities of these salts in pure water (pH 7.0) were determined using high-performance liquid chromatography (HPLC) at 310 K, with the salts showing considerably greater solubility than ciprofloxacin itself and, interestingly, ciprofloxacin/fumaric acid (2:1) being more soluble than ciprofloxacin/fumaric acid (1:1). Intrigued by this phenomenon, we undertook a comparison of the crystal structures of the salts: the three-dimensional sandwich-like structure observed in the 2:1 salt indicates that the preferred stacking may be a factor in increasing the solubility of ciprofloxacin.

Isostructurality Among 5 Solvatomorphs of Betulin: X-Ray Structure and Characterization

Betulin (BE), a triterpene found in many plant species, has recently attracted the attention of researchers because of its important physiological and pharmacological properties, such as anti-HIV and anticancer activities. Studies have revealed the solvatomorphism of BE (I with dimethyl sulfoxide and III with ethanol, named by author), which means more solvatomorphs may be obtained when different solvents are used during crystallization. After solid-form screening tests, 3 new solvatomorphs of BE with methanol (II), n-propanol (IV), and isopropanol (V) were obtained. In this work, 5 BE solvatomorphs were characterized by X-ray powder diffractometric, thermogravimetric, and Fourier transform infrared spectroscopic analyses. Single-crystal X-ray diffraction was used to analyze the X-ray structures of the compounds, and all 5 solvatomorphs were proven to be isostructral. Change in the crystal symmetry, intermolecular arrangements, stoichiometry, and hydrogen bonding interactions of the solvatomorphs resulted from solvent incorporation to the solvates. Solvatomorphs II, IV, and V, along with their single-crystal structures, were reported for the first time.

Development of a new ferulic acid certified reference material for use in clinical chemistry and pharmaceutical analysis

This study compares the results of three certified methods, namely differential scanning calorimetry (DSC), the mass balance (MB) method and coulometric titrimetry (CT), in the purity assessment of ferulic acid certified reference material (CRM). Purity and expanded uncertainty as determined by the three methods were respectively 99.81%, 0.16%; 99.79%, 0.16%; and 99.81%, 0.26% with, in all cases, a coverage factor (k) of 2 (P=95%). The purity results are consistent indicating that the combination of DSC, the MB method and CT provides a confident assessment of the purity of suitable CRMs like ferulic acid.

Development of a new chlorogenic acid certified reference material for food and drug analysis

&NA; This paper reports the preparation and characterization of a new chlorogenic acid (CHA) certified reference material (CRM), which is unavailable commercially. CHA is an active ingredient found in many geo‐authentic Chinese medicinal materials and developed as an anti‐cancer drug. In this work, trace impurities were isolated and identified through various techniques. CHA CRM was quantified with two analytical methods, and their results were in good agreement with each other. The certified value and corresponding expanded uncertainty of CHA CRM reached 99.4% ± 0.2%, which was calculated by multiplying the combined standard uncertainty by the coverage factor (k = 2), at a confidence level of 95%. This CRM can be used to calibrate measurement system, evaluate or validate measurement procedures, assign traceable property values to non‐CRMs, and conduct quality control assays. Graphical abstract Figure. No caption available. HighlightsA new chlorogenic acid certified reference material was developed, including the preparation and characterization.Two impurities were found, namely isochlorogenic acid and chlorogenic acid methylester, respectively.The CRM was quantified with two analytical methods, and their results were in good agreement with each other.

Study on four polymorphs of bifendate based on X-ray crystallography.

Bifendate, a synthetic anti-hepatitis drug, exhibits polycrystalline mode phenomena with 2 polymorphs reported (forms A and B). Single crystals of the known crystalline form B and 3 new crystallosolvates involving bifendate solvated with tetrahydrofuran (C), dioxane (D), and pyridine (E) in a stoichiometric ratio of 1:1 were obtained and characterized by X-ray crystallography, thermal analysis, and Fourier transform infrared (FT-IR) spectroscopy. The differences in molecular conformation, intermolecular interaction and crystal packing arrangement for the four polymorphs were determined and the basis for the polymorphisms was investigated. The rotation of single bonds resulted in different orientations for the biphenyl, methyl ester and methoxyl groups. All guest solvent molecules interacted with the host molecule via an interesting intercalative mode along the [1 0 0] direction in the channel formed by the host molecules through weak aromatic stacking interactions or non-classical hydrogen bonds, of which the volume and planarity played an important role in the intercalation of the host with the guest. The incorporation of solvent-augmented rotation of the C–C bond of the biphenyl group had a striking effect on the host molecular conformation and contributed to the formation of bifendate polymorphs. Moreover, the simulated powder X-ray diffraction (PXRD) patterns for each form were calculated on the basis of the single-crystal data and proved to be unique. The single-crystal structures of the four crystalline forms are reported in this paper.

Development of a new tetrandrine certified reference material for clinical chemistry and pharmaceutical analysis

Certified reference materials (CRMs) with good metrological characteristics are essential tools to guarantee the reliability and validity of analytical measurements. However, in the research field of medical treatment and public health, compared with the number of marketed drugs or related medical products, the number of CRMs for clinical chemistry and pharmaceutical analysis is very limited. Based on this situation, a study towards a new tetrandrine CRM was carried out according to ISO guides 34 and 35. The study includes sample purification, homogeneity testing, stability study, characterization, and uncertainty evaluation. In the characterization of tetrandrine CRM, two methods based on different principles, namely, mass balance (MB) and differential scanning calorimetry (DSC) methods, were employed based on recommendations of the respective ISO Guides. The certified value of tetrandrine CRM is 99.7% with an expanded uncertainty of (+0.3%, −0.6%) (k = 2, P = 0.95). The tetrandrine CRM has been approved and assigned as a primary reference material and numbered as GBW 09544.

Structural and Computational Study of 4 New Solvatomorphs of Betulin: A Combined X-Ray, Hirshfeld Surface, and Thermal Analysis

Four new solvatomorphs of betulin were reported and characterized by X-ray diffractometry as well as thermal and vibrational spectroscopic analyses. Single-crystal X-ray diffraction was used to analyze the X-ray structures of the compounds and confirmed the stoichiometric ratio between the host and guest molecules from thermal data. Results indicated that solvatomorphism occurred in several betulin solvates. Changes in intermolecular arrangements, stoichiometry, and hydrogen-bonding interactions of solvatomorphs were due to solvent incorporation to solvates. Hirshfeld surface analyses, especially dnorm surface and fingerprint plots, were used to determine intermolecular interactions in the crystal network. Solvent molecules played an important role in the construction of a 3D architecture. The stabilities of these solvates were evaluated by thermal analyses. Nonisothermal kinetic analysis was used to explain the kinetics of solid-solid phase transition (desolvation) of betulin solvates. The apparent activation energies were evaluated using Kissinger and Ozawa methods. Moreover, phase transitions were visually investigated by hot-stage microscopic analysis.

Certification of reference materials for analysis of isoflavones genistin and genistein in soy products

Soy isoflavones are a class of secondary metabolites in the growth process of soybeans or other legumes. Many studies support their roles in the prevention and treatment of cancer, arterial sclerosis, osteoporosis and menopausal syndrome. Genistin and genistein, the two highest amount active ingredients in soy isoflavones, were developed into two new certified reference materials (CRMs) in this work. According to the guidelines of development of CRMs, mainly ISO Guides 34:2009 and 35:2005, studies on sample preparation, homogeneity, stability, characterization, and uncertainty estimation were carried out. In the characterization, two methods based on different theories, namely differential scanning calorimetry (DSC) and coulometric titrimetry (CT), were employed. Genistin and genistein CRM certified values and corresponding expanded uncertainties, obtained from the combined standard uncertainty multiplied by the coverage factor (k = 2), for a confidence level of 95%, were 99.7 ± 0.3% and 99.3 ± 0.5%. The mass balance (MB) method was employed to cross-check the results. Genistin and genistein CRMs have been approved and assigned as a grade primary reference material by the National Administrative Committee. These CRMs can be applied to the analysis of soy isoflavones in related products, such as (fermenting) soybean foods or medicines.