In vivo determination of the bioavailability of folic acid through the utilization of the PBPK model in conjunction with UPLC.

This paper employed a physiologically based pharmacokinetic model (PBPK) to investigate the transformations of folic acid and its metabolites in vivo. Additionally, an ultra-performance liquid chromatography (UPLC) method was developed to accurately measure the body's retention rate and conversion rate of folic acid, tetrahydrofolate, and 5-methyltetrahydrofolate. Furthermore, the bioavailability of folic acid in the body was assessed by combining this method with an evaluation technique for animal models. The study found that the gastric metabolism time was 2 h, while the small intestinal metabolism duration was 4 h. The maximum conversion rate was observed in plasma and liver after 6 h, and in the brain after 8 h. This serves as a framework for creating a model to assess the bioavailability of folic acid in living organisms, to enhance the safety and efficacy of folic acid intake.

[Qualitative and semiquantitative analyses of the chemical components of the seed coat and kernel of Ziziphi Spinosae Semen].

Ziziphi Spinosae Semen refers to the dried seed of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou. The seed is composed of a reddish brown coat and a yellow kernel. A comparative study was conducted to investigate differences in the chemical composition and their relative contents between the seed coat and kernel of Ziziphi Spinosae Semen. First, the chemical compounds found in the seed coat and kernel were characterized and identified using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The analytical results tentatively identified 57 chemical compounds based on reference-compound comparison, literature retrieval, and chemical-database (e. g., MassBank) searches; these compounds included 14 triterpenes, 23 flavonoids, 7 alkaloids, 6 carboxylic acids, and 7 other types of compounds. The mass error of the identified compounds was within the mass deviation range of 5×10-6 (5 ppm). Next, two methods of multivariate statistical analysis, namely, principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), were used to compare the differential compounds between the two seed parts. A total of 17 differential compounds were screened out via OPLS-DA based on a variable importance in projection (VIP) value of >5. The results revealed that betulinic acid, betulonic acid, alphitolic acid, and jujuboside Ⅰ mainly existed in the seed coat whereas the 13 other compounds, such as spinosin, jujuboside A, and 6‴-feruloylspinosin, mainly existed in the seed kernel. Therefore, these 17 differential compounds can be used to distinguish between the two seed parts. Finally, a semiquantitative method was established using UPLC and a charged aerosol detector (CAD) with inverse gradient compensation in the mobile phase. Six representative compounds with different types were selected to examine the CAD response consistency: magnoflorine (alkaloid), spinosin (flavone), 6‴-feruloylspinosin (flavone), jujuboside A (triterpenoid saponin), jujuboside B (triterpenoid saponin), and betulinic acid (triterpenoid acid). The results showed that the relative standard deviation (RSD) of the average response factors at different levels of these six compounds was 7.04% and that their response intensities were similar. Moreover, each compound in the fingerprint demonstrated good response consistency, and the peak areas obtained directly reflected the contents of each compound. Based on the semiquantitative fingerprints obtained, betulinic acid and oleic acid were considered the main components of the seed coat. The betulinic acid content in the seed coat was approximately 7 times higher than that in the seed kernel. Spinosin, jujuboside A, linoleic acid, betulinic acid, and oleic acid were the main components of the seed kernel. The spinosin content in the seed kernel was 18 times higher than that in the seed coat. In addition, the jujuboside A content in the seed kernel was 24 times higher than that in the seed coat. The proposed method can accurately determine the main components and compare the relative contents of these components in different seed parts. In summary, this study identified the differences in chemical components between the seed coat and kernel of Ziziphi Spinosae Semen and clarified the main components and their relative contents in these parts. The findings can not only provide a basis for the identification of chemical compounds and quality research on different parts of Ziziphi Spinosae Semen but also promote the development and utilization of this traditional Chinese medicine.

Evaluation of In Vivo Folic Acid Bioavailability in Different Mouse Strains Using Enzymatic Digestion Combined with Ultra Performance Liquid Chromatography.

By analyzing the folic acid content of various mouse strains through the use of in vivo studies, this study sought to determine whether folic acid bioavailability varies between hosts. In order to examine the stability of folic acid in the gastrointestinal tract, the rate at which it enters the blood, its retention in the organs, and its entry into the brain, folic acid was gavaged for 10 days into male and female mice of the following four strains: C57BL/6, BALB/c, ICR, and Kunming. Folic acid was extracted from eight groups of mice via solid phase extraction and triple enzyme extraction; the folic acid was subsequently quantified by ultraperformance liquid chromatography. In contrast to the other groups, female C57BL/6 mice exhibited substantially greater bioavailability as well as variations in organ retention and blood entry rates, as indicated by the experimental findings. This finding indicated that using female C57BL/6 mice to evaluate the bioavailability of folic acid is more effective.