Journal of separation science最新文献

Advances in techniques for quality analysis allow for a more detailed examination of drug impurities. High-resolution mass spectrometry (HRMS) contributes to detecting both known and unknown impurities. In this study, a combination of a nontargeted and targeted screening approach was established and applied to the detailed degradation profile of the losartan potassium (LP) drug substance. Through general unknown comparative screening (GUCS), 35 degradation products (DPs) were detected; of these, 10 DPs were confirmed with reference substances. DP-1, DP-2, DP-3, and DP-6 were the first characterized, as per previous studies; the other twenty-four were newly identified. In addition, a liquid chromatography-tandem mass spectrometry method was developed for the determination of the ten DPs. It was sensitive, with the limit of quantitation of analytes ranging from 0.01 to 0.5 ng mL⁻¹. Two newly characterized DPs, DP-1 and DP-2, were determined in active pharmaceutical ingredient solutions. This study introduced a new approach using broad screening to analyze degradation impurity profiles in LP drug substance, aiding in the identification of low-level impurities or those without reference substances. Additionally, the sensitive determination method developed allows for the precise quantification and control of ten DPs at trace levels in LP drug substances or products.

Shenfu Qiangxin (SFQX) pills are proprietary traditional Chinese medicine used for the treatment of chronic heart failure with significant clinical effects. However, the systematic identification and quantification of complexed components in SFQX have not been reported yet. In this work, a reliable and comprehensive method for a rapid identification of chemical components was developed by data dependent acquisition using ultra performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-Q Exactive-Orbitrap-MS). A total of 104 compounds mainly including flavonoids, saponins, alkaloids, anthraquinones, coumarins, and phenolic acids were identified through database searching. The identified compounds were further ascribed to herb species in SFQX pills, such as Ginseng Radis et Rhizoma, Aconiti Lateralis Radix Praeparata (processed), Mori Cortex, Lepidii Semen, Rhei Radix et Rhizoma, and Polyporus. Thirty-two representative compounds were elaborated with cleavage pathways and characteristic fragments in MS/MS spectrum of commercially available standards. A quantification method based on parallel reaction monitoring technique was established, and absolute quantification of 28 components in SFQX pills was then carried out. This work constitutes a basis and methodological reference for the quality control, consistency evaluation, and standardization of similar proprietary Chinese medicines.

Wutou decoction is an ancient compound preparation composed of five herbal medicines, which has good therapeutic effects on rheumatoid arthritis. There are two classic preparation methods of Wutou decoction using honey and water as decocting excipients, respectively. However, the differences of chemical compositions between these two Wutou decoctions yet remain unclear. Therefore, honey-decocting Wutou decoction was prepared according to the record written in Synopsis of Golden Chamber, and water-decocting Wutou decoction was prepared by the process commonly used in clinics nowadays. Wutou decoction database was also established for the identification of their chemical compositions. Ultrahigh–performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry technique combined with chemometric analysis was further established and applied to analyze their chemical compositions. A total of 128 components were identified in honey-decocting Wutou decoction, whereas 126 components in water-decocting Wutou decoction. Isoguanosine and aromadendrin were found to exist only in honey-decocting Wutou decoction, but not in water-decocting Wutou decoction. Principal component analysis results showed that there were obvious differences between honey-decocting Wutou decoction and water-decocting Wutou decoction. Orthogonal partial least squares discriminant analysis further verified these differences, of which 30 potential differential components were found by calculation of their variable importance in the projection values. Different chemical compositions will inevitably affect the toxicity and safety of Wutou decoction, and it is imperative to calibrate its preparation process.

Periodontitis is a chronic inflammation of the periodontal support tissues. The typical symptoms of periodontitis are inflammation and alveolar bone resorption. Chitong Xiaoyanling Granules (CXG) is composed of 10 Chinese herbs, which have the efficacy of dispersing wind, clearing heat, cooling blood, and relieving pain. CXG is clinically used for the treatment of periodontitis and other diseases, with remarkable efficacy and broad application prospects. However, due to the lack of systematic research on its chemical constituents and metabolites, it is of great significance to characterize the various chemical components and metabolites of CXG. In this study, ultra-high-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry analysis was used to identify the chemical constituents and metabolites of CXG, and the differences in metabolite profiles between normal and model rats were compared. A total of 147 compounds were identified in CXG, including 53 flavonoids, 28 terpenoids, seven chromones, eight coumarins, eight organic acids, 12 phenols, 10 alcohols, nine sugars, and 12 others. In normal and model rats, 191 and 179 CXG-related xenobiotics were detected respectively. In conclusion, a rapid and accurate identification method was used to identify the chemical components and metabolites of CXG, which laid a foundation for the study of the quality control and pharmacological mechanisms of CXG.

Jabuticaba (Plinia cauliflora) is a typical subtropical Brazilian fruit with unique organoleptic properties and a high nutritional value. This study shows a qualitative analysis of jabuticaba peels with volatile and semi-volatile components harvested from Minas Gerais, Brazil. A new device, the hydrophilic microporous cartridge, was developed to extract jabuticaba peels' volatile/semi-volatile components using a solid-phase microextraction method by direct immersion. This cartridge protected the polymer phase fiber, preventing its breakage and impregnation of the material. The developed method is simple, using a few steps to prepare jabuticaba peel samples. The fiber selected for analysis was a divinylbenzene/carboxene/polydimethylsiloxane of 30/50 µm. A comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry system was used to analyze natural products in jabuticaba peels. The method was optimized by a factorial design and could detect 213 organic compounds. Of particular note is the detection of terpenes (33.27%), fatty acids (29.60%), and ethyl esters (9.23%), which are mainly responsible for the nutritional properties and odor of the fruit. This study presents an improved method for extracting volatile compounds, offering enhanced insights into the phytochemical composition, aroma, flavor, and bioactivity of jabuticaba.

Fagopyri Dibotryis Rhizoma, a traditional Chinese medicine, is widely used to treat various ailments such as pulmonary abscesses, measles pneumonia, and swelling. Its notable therapeutic effects are closely related to the chemical constituents, making it crucial to conduct in-depth research on the chemical components. In this study, a total of 209 compounds were preliminarily identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry in Fagopyri Dibotryis Rhizoma. Subsequently, a method was established using ultra-high-performance liquid chromatography-triple quadrupole/linear ion trap tandem mass spectrometry for the simultaneous determination of 24 main ingredients (flavonoids and phenolic acids) in Fagopyri Dibotryis Rhizoma from different habitats and growing periods. Quantitative results showed that different compounds displayed varying contents across different habitats, with catechin, epicatechin, procyanidin B2, and procyanidin C1 being relatively abundant. Principal component analysis and partial least squares discriminant analysis showed there were significant differences among Fagopyri Dibotryis Rhizoma from different habitats, and the quality from Yunnan was superior. Entropy weight TOPSIS analysis showed that Fagopyri Dibotryis Rhizoma grown until late October has better comprehensive quality, which is basically consistent with the traditional harvesting time. In summary, this study can provide reference methods for the comprehensive evaluation of the quality of Fagopyri Dibotryis Rhizoma.

Dopamine and serotonin are neurotransmitters that are crucial for numerous physiological processes, including mood regulation, reward, and motor function. Dysregulation of these neurotransmitters is associated with various neuropsychiatric disorders. Albumin in plasma modulates the bioavailability of drugs and free concentrations of bioactive constituents. This study aimed to characterize the interactions of dopamine and serotonin with bovine serum albumin. Capillary electrophoresis in the frontal analysis mode was utilized as an effective method to assess dopamine–bovine serum albumin and serotonin–bovine serum albumin affinity. The free neurotransmitter plateaus were distinctly separated from the bovine serum albumin–neurotransmitter complex plateaus. Free dopamine and serotonin concentrations were determined by monitoring the heights of their respective plateaus. In contrast, the bound concentrations were calculated from the difference between the total and free plateau heights. Dopamine and serotonin were found to bind to bovine serum albumin at independent sites with binding constant values of 1.90 × 10³ and 2.90 × 10³ L/mol, respectively. Additionally, an in silico molecular docking approach revealed the binding sites for dopamine and serotonin near the glutamic acid-291 and serine-428 residues of bovine serum albumin, respectively.

Taking Citri Reticulatae Pericarpium (CRP) as an example, it is proved that there are differences between the powder decoction and pieces decoction of traditional Chinese medicine (TCM). In this study, an ultra-high performance liquid chromatography quadrupole exactive orbitrap MS/MS (UHPLC-Q-Exactive Orbitrap MS/MS) method was established to characterize 80 chemical components of CRP. The content of components was compared based on extraction rate, alcohol solubility rate, and mass spectrum peak area. The result showed that the content in CRP powder decoction was generally higher than that in CRP pieces decoction. The principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to distinguish between the two decoctions. In addition, cardiovascular diseases (CVDs) were used as a model to investigate whether the increased content of components has practical significance. Network pharmacology screened five core targets of CRP in CVDs. The results of molecular docking indicated that the binding energies were all ≤ −5.0 kcal/mol between effective compounds (M34, M57, M80, etc.) and key targets (Akt1, SRC, ESR1, EGFR, and PTGS2) with good affinity. These results provide an important reference for further development and use of CRP powder decoction.

Lenvatinib has been demonstrated effective in advanced hepatocellular carcinoma (HCC), but the pharmacokinetic–pharmacodynamics behavior of lenvatinib and its metabolites remains unclear. To investigate the pharmacokinetic–pharmacodynamics behavior of lenvatinib and its active metabolites in advanced HCC patients, it is important to develop a simple and rapid method to analyze the exposures of lenvatinib and its metabolites in human samples. Here, we established and validated a simple and rapid method for determining lenvatinib and its three major metabolites, descyclopropyl lenvatinib (M1), O-demethyl lenvatinib hydrochloride (M2), and lenvatinib N-Oxide (M3) by liquid chromatography-tandem mass spectrometry method. Lenvatinib and its main metabolites were separated on an X-Terra RP18 column (50 × 2.1 mm, 3.5 µm) at 35°C within 3 min, and the analytes were isocratically eluted with the mobile phase of methanol–water (10:90, v/v) containing 0.1% of formic acid at a flow rate of 0.15 mL/min. The calibration range was 1–1000 ng/mL for lenvatinib, while 0.1–100 ng/mL for M1–M3 under positive electrospray ionization mode. The inter- and intra-batch precisions and accuracy were acceptable for lenvatinib and its metabolites. This method was successfully applied to measure lenvatinib and its metabolites in plasma samples from HCC patients, which provides a robust tool for pharmacokinetic–pharmacodynamics studies of lenvatinib.