Evaluation of the stability of polyamines in human serum at different storage temperatures using capillary electrophoresis with indirect ultraviolet detectionSilva, Ana Paula; Nishida, Sônia; Calixto, Leandro Augusto; Silva, Heron Dominguez Torres; Moraes, Maria Lourdes Leite
doi: 10.1002/bmc.5601pmid: 36775344
Polyamines are low molecular weight compounds that are present in all living organisms. They are related to the pathological processes, and have been studied as biomarkers for tumor progression, being analyzed in patients’ biological fluids. However, polyamines can undergo degradation in serum samples, depending on storage conditions, which impairs their quantification in these matrices. In this work, capillary electrophoresis using indirect ultraviolet detection has been developed and applied to evaluate the stability of polyamines [cadaverine (Cad), putrescine (Put), spermine (Spm), and spermidine (Spd)] in human serum at different storage temperatures. By using this method, Cad, Put, Spm, and Spd were separated in less than 4 min. The range of the correlation coefficients was 0.993–0.998. The corresponding limits of detection and quantification were as follows (in mg L–1): Spm: 0.209 and 0.697; Spd: 0.165 and 0.549; Put: 0.189 and 0.632; Cad: 0.125 and 0.417. Besides, the coefficient of variation was lower than 1% for all analytes and the recovery was 92%–110%. The method was successfully applied for polyamines spiked in human serum samples from healthy people. The results showed that the degradation of polyamines was lower in samples stored in a freezer (−20°C).
Integrated UPLC–Q‐TOF–MS and network pharmacology approach‐driven quality marker discovery of Danggui Shaoyao San for primary dysmenorrheaLi, Zhe; Xiong, Hui; Li, Na; Zhao, Lanqingqing; Liu, Zi; Yu, Yongzhou; Zhao, Chunying
doi: 10.1002/bmc.5608pmid: 36805594
Danggui Shaoyao San (DSS), a famous prescription, has been clinically proved to be effective in treating primary dysmenorrhea (PD). Currently there is no valid quality control data available for DSS. The main aim of the current research was to explore quality markers (Q‐markers) of DSS. The chemical constituents of DSS were qualitatively identified using ultra‐performance liquid chromatography tandem quadrupole time of flight mass spectrometry (UPLC–Q‐TOF–MS) technology. On this basis, the targets of DSS and PD were predicted and screened using the TCMSP, SwissTargetPrediction, GeneCards, OMIM and TTD databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed on the core intersection targets using string and Cytoscape 3.7.1 software. Then molecular docking was conducted to screen the Q‐markers of DSS in PD. A total of 126 chemical constituents, including 22 organic acids, 14 phthalides, 24 monoterpenoids, five sesquiterpene lactones, 22 triterpenoids, four phenylpropanoids and 35 other compounds were preliminarily characterized. According to network pharmacology prediction analysis, six compounds containing polyporenic acid C, senkyunolide P, alisol B 23‐acetate, naringenin, gallic acid, ferulic acid and albiflorin were regarded as Q‐markers of DSS. The present research established an integrative UPLC–Q‐TOF–MS and network pharmacology method to discover the latent Q‐markers of DSS and provided a theoretical data for the follow‐up quality control of DSS.
Quantitative determination of plasma cabozantinib concentration using HPLC–UV and its application to patients with renal cell carcinomaMaruyama, Shinichi; Kato, Masaru; Hiraga, Tatsuru; Ishida, Masaru; Kanno, Hiroshi
doi: 10.1002/bmc.5599pmid: 36760165
Cabozantinib is an oral small‐molecule tyrosine kinase inhibitor that has become a standard of care for advanced renal cell carcinoma (RCC). However, cabozantinib is associated with a high rate of adverse events. Therefore, individualised cabozantinib administration and monitoring could help maximise its therapeutic efficacy and avoid serious adverse events. This study developed and validated a method to determine cabozantinib concentration in plasma using HPLC–UV. Sorafenib, an internal standard, was added to the plasma sample containing cabozantinib. A calibration curve for cabozantinib showed good linearity (R2 = 1.00), between 25 and 4,000 ng/ml. The recovery rate was above 92.1%, and the intra‐ and inter‐day coefficients of variation were smaller than 5.2 and 6.8%, respectively. Then, we applied the method for monitoring cabozantinib blood levels in three patients with advanced RCC who were taking cabozantinib at a dose of 20, 40 or 60 mg/day. Grade 3 adverse events were more likely to occur in patients with high dosing and blood level of cabozantinib. Owing to its simplicity, the developed method can be used in general hospitals, and is expected to help maximise drug efficacy and minimise serious adverse events in many patients with RCC undergoing cabozantinib treatment.
Preparation, characterization, and pharmacokinetics of oridonin‐loaded liposomesLin, Fei‐er; Zhang, Xin‐yan; Zhang, Yu‐ping; Wang, Jin
doi: 10.1002/bmc.5603pmid: 36781382
The aim of this study was to prepare oridonin liposomes and evaluate the physicochemical characteristics and pharmacokinetics in rats. A three‐level, three‐factor Box–Behnken design was used to optimize the preparation of oridonin liposomes. A highly sensitive high‐performance liquid chromatographic quantification method using ultraviolet detection was established and validated for the determination of oridonin in rat plasma. Twelve Sprague–Dawley rats were randomly assigned and injected with 15 mg/kg of oridonin or oridonin liposomes via the tail vein. Pharmacokinetic parameters were estimated using a compartmental modeling approach using PKsolver software. The optimum conditions were as follows: soybean phospholipids/cholesterol ratio, 3.9:1; soybean phospholipids/drug ratio, 8.5:1; and soybean phospholipid concentration, 1.1%. Under these conditions, the mean particle size, polydispersity index, zeta potential, and encapsulation efficiency of oridonin liposomes were 170.5 nm, 0.246, −30.3 mV, and 76.15%, respectively. The pharmacokinetic results showed that liposomes could significantly prolong the elimination half‐life (from 2.88 ± 0.55 to 13.67 ± 3.52 h), increase the area under the concentration–time curve (from 1.65 ± 0.17 to 6.22 ± 0.83 μg h/ml), and decrease the clearance (from 6.62 ± 1.38 to 1.96 ± 0.24 L/kg h). The oridonin liposomes increased the elimination half‐life and area under the concentration–time curve and provided a reference for the development of drugs with a short half‐life.
The tissue distribution of Jinzhen oral liquid in healthy and influenza miceChen, Xialin; Gao, Xia; Cao, Liang; Wang, Shanli; Qian, Mengyu; Tong, Xiaoyu; Wang, Jiajia; Gao, Huifang; Wang, Zhenzhong; Li, Jifeng; Xiao, Wei
doi: 10.1002/bmc.5605pmid: 36793147
Jinzhen oral liquid (JZOL) is widely used in China. However, its tissue distribution, a vital part of the efficacy substances research, has not been reported yet. This study characterized its chemical components and its prototypes and metabolites in mice, and investigated its tissue distribution in pathological and healthy mice. Several constituents were characterized, including 55 constituents in JZOL, 11 absorbed prototypes and six metabolites in plasma and tissues. The metabolic pathways were demethylation, dehydration and acetylation. A sensitive, accurate and stable quantitative method was established and applied to the tissue distribution. After administration of JZOL, these seven components were rapidly distributed to various tissues, mainly staying in the small intestine, and less distributed to lung, liver and kidney. Compared with healthy mice, the absorption of baicalin, wogonoside, rhein, glycyrrhizic acid and liquiritin apioside was reduced in influenza mice, but their elimination was slow. However, influenza infection had no obvious effect on the overall distribution of the most important components (baicalin, glycyrrhizic acid and wogonoside) in the plasma or small intestine, but obviously affected the distribution of baicalin in liver. In summary, seven components are rapidly distributed to various tissues, and influenza infection has certain influence on the tissue distribution of JZOL.
A simple and sensitive LC–MS/MS method for the determination of polyphyllin VII in rat plasma and its application to pharmacokinetic studyWang, Hao; Han, Han; Xu, Ying; Yang, Yishun
doi: 10.1002/bmc.5597pmid: 36750761
Polyphyllin VII is an isoprene saponin extracted from Rhizoma paridis, and it can effectively suppress tumor initiation, growth, and metastasis. In this study, we aim to develop and validate an LC–MS/MS method for the quantification of polyphyllin VII in rat plasma using digoxin as the internal standard (IS). The plasma samples were precipitated with methanol, and the samples were separated on an ACQUITY BEH C18 column (2.1 × 50 mm, 1.7 μm). The mobile phase consisted of 0.1% formic acid solution and acetonitrile. The detection was performed in the multiple reactions monitoring mode, with the precursor‐to‐product transitions of m/z 1075.4 > 883.3 for polyphyllin VII and m/z 779.4 > 649.6 for the IS. The method showed excellent linearity over the concentration range of 0.5–1000 ng/ml, with a correlation coefficient of 0.9996 (r = 0.9996). The lower limit of quantification was 0.5 ng/ml. The inter‐ and intra‐day accuracy (relative error) ranged from −4.8 to 5.9%, and precision (relative standard deviation) was < 9.0%. The assay showed high extraction recovery, ranging from 90.6 to 95.6%. Polyphyllin VII was demonstrated to be stable under the storage conditions. The validated LC–MS/MS method was successfully applied to the pharmacokinetic study of polyphyllin VII in rats after oral, intraperitoneal, and intravenous administrations. The pharmacokinetic results indicated that polyphyllin VII showed low oral (5.86%) bioavailability and moderate (38.81%) intraperitoneal bioavailability.
Qualitative and quantitative method for quality control of Itea ilicifolia based on antioxidant Q‐markersFeng, Yunqian; Zhang, Pan; Yang, Yaxin; Wang, Zhiwei; Luo, Guoyong; Yang, Wude
doi: 10.1002/bmc.5594pmid: 36735642
Itea ilicifolia Oliv is a folk medicine with antioxidant potential. In this study, the fingerprints of 14 batches of I. ilicifolia were established by HPLC with 17 common peaks. The similarities evaluated by Similarity Evaluation System for Chromatographic Fingerprint of Chinese Materia (version 2012) were >0.89. Ten compounds were identified with definite structures by comparing the retention time and characteristic UV spectral pattern with those of reference substances. The antioxidant capacities of 14 batches of I. ilicifolia were evaluated based on O2·−, DPPH and ABTS·+ radical scavenging assays in combination with ferric reducing antioxidant power assay. Via multivariate statistical analyses of gray relation analysis, bivariate correlation analysis and partial least squares regression analysis, a study on the spectrum–effect relationship was then performed to screen eight peaks as the antioxidant Q‐markers of I. ilicifolia. The contents of representative antioxidant Q‐markers (isoorientin, orientin, vitexin, isovitexin and iteafuranal A) in samples were accurately determined to be 0.054–0.118%, 0.034–0.080%, 0.018–0.055%, 0.031–0.091% and 0.033–0.140%, respectively. The qualitative and quantitative analytical method based on Q‐markers helps to control the antioxidant quality of I. ilicifolia, which will lay the foundation to promote the rational utilization of I. ilicifolia in curing diseases related to oxidative stress.
Metabolomic analysis of the sera of patients with the long‐term inhalation of caffeine‐sodium benzoate using LC–MSYu, Tianwei; Yan, Quanzhi; Tian, Lili; Zhao, Huiying; Suo, Feiya; Suriguga, ; Li, Weixin; Guo, Rong; Yang, Hao
doi: 10.1002/bmc.5567pmid: 36515669
The present study aimed to systematically assess the potential biomarkers in the serum samples of patients with long‐term inhalation of caffeine‐sodium benzoate (CSB). LC–MS was applied to analyze the metabolic profiles of serum samples of patients with the long‐term intake of CSB (n = 35) and other volunteers with no intake of CSB treated as the control group (n = 35). The raw data of metabolic profiles were analyzed via principal component analysis, partial least squares analysis, and orthogonal partial least squares analysis. MBRole 2.0 online tools were used to analyze the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of different metabolites. The serum metabolic profiles showed several metabolites with large variations, including 2‐propyl‐2,4‐pentadienoic acid, 24‐hydroxycholesterol, 3‐O‐sulfogalactosylceramide (d18:1/24:1(15Z)), 3‐O‐sulfogalactosylceramide (d18:1/12:0), 3‐O‐sulfogalactosylceramide (d18:1/14:0), 3a,7a‐dihydroxy‐5b‐cholestan‐26‐al, 3a,7a‐dihydroxy‐5b‐cholestane, 7a,25‐dihydroxycholesterol, bilirubin, and dehydroepiandrosterone sulfate. The Kyoto Encyclopedia of Genes and Genomes pathways involved in metabolism included ‘choline metabolism in cancer’ and ‘glycerophospholipid metabolism’. In conclusion, the present study provides a basis with which to explore the molecular‐specific mechanisms concerning the effects of the long‐term inhalation of CSB on human physical and mental health.