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Heliyon · 2023 · IF 4

Determination of nine cardiovascular drugs in human plasma by QuEChERS-UPLC-MS/MS

Chengcheng Jin,Ting Wang,Tingting Zhao,Wen Jiang,Xiaolan Zhen,Hui Li

Objective To determine the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma through QuEChERS pre-treatment combined with ultra-performance liquid chromatography-tandem mass spectrometry. Plasma samples were extracted with 3 mL of acetonitrile, 400 mg of anhydrous magnesium sulfate as a salting agent, and 20 mg of C18 as a sorbent. An Agilent Poroshell 120 EC-C18 column (4.6 × 100 mm, 2.7 μm) was selected and methanol-0.1 % water was used as the mobile phase, and ESI positive ion detection mode was selected. Results: The plasma concentrations of nisoldipine, metoprolol, and prazosin exhibited good linearity within the range of 0.05–4.0 ng/mL (r > 0.99), while atenolol, bisoprolol, propranolol, rosuvastatin, and atorvastatin showed linearity within the range of 0.5–40 ng/mL (r > 0.99). Fluvastatin showed good linearity within the range of 5.0–400 ng/mL. The accuracy of the method ranged from 94.15 to 110.62 %, while the recovery levels were in the range of 85.23 %–115.13 %. The matrix effects were observed between-6.54 % and 12.43 %. The intra-day and inter-day RSD was <15 % for the three concentrations of low, medium, and high. Conclusion The proposed method is rapid, accurate, specific, simple, reproducible, and suitable for the simultaneous measurement of the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma.

研究领域: 分析化学 · 药理学 · 临床医学
✓ 已验证 DOI 高影响因子
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Chemistry Central Journal · 2014 ·Vol. 8 ·期 1 ·1-10 · IF 1.663

Validated method to measure yakuchinone A in plasma by LC-MS/MS and its application to a pharmacokinetic study in rats

Chen Feng,Li Hai-Long,Tan Yin-Feng,Guan Wei-Wei,Li Yong-Hui,Zhang Jun-Qing

Background Yakuchinone A has a plethora of beneficial biological effects. However, the pharmacokinetic (PK) data of yakuchinone A still remain unknown so far. Furthermore, the quantification of yakuchinone A in biological samples has not been reported in the literature. Therefore, in the present study we aimed to develop a new method for the fast, efficient and accurate assessment of yakuchinone A concentration in plasma, as a means for facilitating the PK evaluation of yakuchinone A.Results A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the determination of yakuchinone A in rat plasma. Mass spectrometric and chromatographic conditions were optimized. Plasma samples were pretreated by protein precipitation with methanol. LC separation was performed on a Phenomenex Luna C18 column with gradient elution using a mobile phase consisting of methanol–water containing 0.5 mM formic acid (HCOOH) at a flow rate of 0.28 mL/min. ESI-MS spectra were acquired in positive ion multiple reaction monitoring mode (MRM). The precursor-to-product ion pairs used for MRM of yakuchinone A and yakuchinone B were m/z 313.1 → 137.0 and 311.2 → 117.1, respectively. Low concentration of HCOOH reduced the ion suppression caused by matrix components and clearly improved the analytical sensitivity. Yakuchinone A showed good linearity over a wide concentration range (r > 0.99). The accuracy, precision, stability and linearity were found to be within the acceptable criteria. This new method was successfully applied to analyze the rat plasma concentration of parent yakuchinone A after a single oral administration of SuoQuan capsules. Low systemic exposure to parent yakuchinone A was observed.Conclusion The proposed method is sensitive and reliable. It is hoped that this new method will prove useful for the future PK studies.

CAS / MDL: 64-18-6
研究领域: 药理学 · 分析化学 · 生物医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMEDICAL CHROMATOGRAPHY · 2023 ·Vol. 37 ·期 8 ·e5656 · IF 1.8

Fluorescent immunochromatography of vancomycin in plasma: A rapid and sensitive quantitative analysis

Minmin Shen,Haiying Gu,Kai Deng,Zhongpeng Li,Yumei Yuan,Yangjin He,Yin Jin,Nengming Lin

Vancomycin (VAN) has a narrow therapeutic window and variable pharmacokinetic properties, which require timely monitoring of plasma concentration to adjust the dosage for better effectiveness. A sensitive and quantitative immunochromatographic method was developed to detect VAN in plasma. The linear response range of the method to detect plasma VAN was 1.25–50 μg/mL. The intra- and inter-assay coefficients were 4.68% and 8.81%, respectively, while the recovery was 89.10%–98.32%. The clinical comparative experiment results demonstrated a good correlation (r > 0.90) between the fluorescent immunochromatographic strip test and the mass spectrum. In this study, a simple, rapid, and high-sensitivity immunochromatographic method was established for detecting VAN, which helped establish the basis for further application of monitoring plasma concentration.

CAS / MDL: 111-30-8
研究领域: 临床药理学 · 分析化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CRYSTAL GROWTH & DESIGN · 2014 · IF 4.558

Pharmaceutical Cocrystals of Ribavirin with Reduced Release Rates

Jia-Mei Chen,Song Li,Tong-Bu Lu

Cocrystals have been extensively utilized to improve drugs’ properties. Ribavirin is a water-soluble broad-spectrum antiviral drug and its application is severely limited by the peak-to-trough fluctuation in plasma drug concentrations and some undesirable side-effects. We show here that formation of cocrystals may be a useful approach to overcome this problem by reducing the release rate of ribavirin. Three cocrystals of ribavirin with 3,5-dihydroxybenzoic acid (1), gallic acid (2), and barbituric acid (3) were successfully prepared and characterized by powder and single crystal X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis, as well as dynamic vapor sorption measurement. The dissolution process revealed that 1–3 showed a reduced release rate as compared to ribavirin in the buffer solution representing intestinal pH 6.8. This study indicates that the release rate of ribavirin can be manipulated over a wide range by the formation of cocrystals, which may subsequently help lower its peak-to-trough fluctuation in plasma concentrations.

CAS / MDL: 99-10-5 149-91-7
研究领域: 药学 · 药物化学
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Journal of Zhejiang University-SCIENCE B · 2018 · IF 1.815

Pharmacokinetic comparison of gossypol isomers in cattle: transfer from diet to plasma and degradation by rumen microbes

Chao-hua Tang,Jia Liu,Qing-yu Zhao,Jun-min Zhang

A pharmacokinetic comparison of gossypol isomers in cattle was made by investigating their transfer from ingested food to plasma and their degradation by rumen microbes. The gossypol isomers in whole cottonseed, plasma, and rumen fluid were determined by high-performance liquid chromatography (HPLC). The intakes of (+)-and (−)-gossypol by cows on three farms were about 5.6–8.5 and 3.8–5.9 g/(d·herd), respectively. The plasma gossypol concentrations increased as ingestion increased and ranged from 0.31 to 0.48 μg/ml for the (+) form and from 0.39 to 0.59 μg/ml for the (−) form. The (+) form was slightly predominant (58.8%–59.8%) in the gossypol ingested by the cows, whereas the (−) form predominated (54.6%–55.9%) in the plasma. An in vitro study showed that at 6 h, 67.4% and 85.7% of the (−)-gossypol were degraded in 500 and 1000 μg/g treatment groups, respectively, and these increased to 83.6% and 92.5%, respectively, at 12 h. The regularity of the degradation of (+)-gossypol was similar to that of (−)-gossypol. These results showed that (−)-gossypol may be more persistent than (+)-gossypol in plasma, and that the degradation of the gossypol isomers in the rumen is rapid and not enantioselective in cattle.

CAS / MDL: 35320-23-1
研究领域: 动物科学 · 药理学
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CLINICA CHIMICA ACTA · 2023 · IF 5

Prognostic value of plasma 7-ketocholesterol in sepsis

Yueyuan Zhang,Sha Xu,Jianxin Xu,Fuchao Xu,Geng Lu,Jiawei Zhou,Shuangshuang Gu,Jun Wang

Background Early evaluation of the severity of sepsis and estimation of its prognosis remains one of the main challenges in current therapeutic strategies. This study aimed to evaluate the prognostic value of plasma 7-ketocholesterol (7-KC) in sepsis. Methods We retrospectively measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) the plasma 7-KC concentration in 176 patients with sepsis and 90 healthy volunteers. A multivariate Cox proportional hazard model was introduced to identify independent factors, including plasma 7-KC and clinical features, for the 28-day mortality of sepsis, and a nomogram for predicting the 28-day mortality of sepsis was established. Decision curve analysis (DCA) was performed to assess the prediction model of death risk of sepsis. Results The area under the curve (AUC) of plasma 7-KC in diagnosing sepsis was 0.899 (95% CI = 0.862–0.935, P < 0.001), while it was 0.830 (95% CI = 0.764–0.894, P < 0.001) in diagnosing septic shock. The AUCs of plasma 7-KC in predicting the survival of sepsis patients in the training cohort and the test cohort were 0.770 (95% CI = 0.692–0.848, P < 0.05) and 0.869 (95% CI = 0.763–0.974, P < 0.05), respectively. In addition, high plasma 7-KC expression predicts poor prognosis in sepsis. Then, 7-KC and platelet count were identified as the two factors with significant differences by a multivariate Cox proportional hazard model, and the 28-day mortality probability ranged from 0.002 to 0.985 and was assessed using a nomogram. DCA results revealed that the combination of plasma 7-KC and platelet count showed the best prognostic efficiency of the risk threshold compared to a single factor in both the training cohort and test cohort. Conclusions Collectively, the elevated plasma 7-KC level is an indicator of sepsis and was identified as a prognostic indicator for sepsis patients, providing a landscape for predicting survival in early sepsis with potential clinical utility.

CAS / MDL: 566-28-9
研究领域: 临床医学 · 生物化学 · 重症医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Analytical Methods · 2023 ·Vol. 15 ·期 33 ·4179-4186 · IF 3.1

Calibration and validation of ultraviolet time-of-flight mass spectrometry for online measurement of exhaled ciprofol

Xiaoxiao Li,Pan Chang,Xing Liu,Zhongjun Zhao,Wenwen Li,Yi Kang,Yixiang Duan,Wensheng Zhang

Ciprofol (HSK 3486, C14H20O), a novel 2,6-disubstituted phenol derivative similar to propofol, is a new type of intravenous general anaesthetic. We found that the exhaled ciprofol concentration could be measured online by ultraviolet time-of-flight mass spectrometry (UV-TOFMS), which could be used to predict the plasma concentration and anaesthetic effects of ciprofol. In this study, we present the calibration method and validation results of UV-TOFMS for the quantification of ciprofol gas. Using a self-developed gas generator to prepare different concentrations of ciprofol calibration gas, we found a linear correlation between the concentration and intensity of ciprofol from 0 parts per trillion by level (pptv) to 485.85 pptv (R2 = 0.9987). The limit of quantification was 48.59 pptv and the limit of detection was 7.83 pptv. The imprecision was 12.44% at 97.17 pptv and was 8.96% at 485.85 pptv. The carry-over duration was 120 seconds. In addition, we performed a continuous infusion of ciprofol in beagles, measured the exhaled concentration of ciprofol by UV-TOFMS, determined the plasma concentration by high-performance liquid chromatography, and monitored the anaesthetic effects as reflected by the bispectral index value. The results showed that the exhaled and plasma concentrations of ciprofol were linearly correlated. The exhaled ciprofol concentration correlated well with the anaesthetic effect. The study showed that we could use UV-TOFMS to provide a continuous measurement of gaseous ciprofol concentration at 20 second intervals.

CAS / MDL: 67-56-1
研究领域: 药理学 · 分析化学 · 麻醉学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BMC INFECTIOUS DISEASES · 2025 ·Vol. 25 ·期 1 ·1-9 · IF 3

Assessment of the impact of different SARS-CoV-2 inactivation operations on colistin sulfate plasma concentration results

Ma Ying-Chao,Yang Xiu-Ling,Gu Jian-Jun

ObjectiveTo evaluate the effects of different SARS-CoV-2 inactivation methods on the blood concentration of colistin sulfate.Methods A colistin sulfate reference substance, a quality control plasma sample, and a clinically measured sample were transferred and heated in a 56 °C water batch for 30 min or irradiated under an ultraviolet (UV) lamp for 60 min to examine the stability of the reference solution and quality control plasma sample. Statistical analysis was conducted for the concentration of the clinically measured sample before and after inactivation with the intraclass correlation coefficient (ICC) method, the Passing–Bablok regression, and the Bland–Altman analysis.Results The reference substance of colistin sulfate was unstable under UV inactivation. Under moist heat inactivation, the reference substance and quality control plasma sample of colistin sulfate were stable. The ICC of the concentration results of 27 clinical blood samples with and without moist heat inactivation was 0.995 (P < 0.001). The Passing–Bablok regression equation was Y = 0.01347 + 0.9861X (R2 = 0.994, n = 27). Finally, 96.30% (26/27) of test data was within the 95% limit of agreement. The results obtained with the three statistical analysis methods all showed a high correlation and agreement between the plasma concentration results of samples not inactivated and inactivated with moist heat inactivation.Conclusion The clinical plasma concentration test samples for colistin sulfate can be processed with the moist heat virus inactivation method to reduce the risk of virus infection of medical staff.

CAS / MDL: 64-18-6
研究领域: 医学 · 药理学 · 病毒学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Marine Drugs · 2022 ·Vol. 20 ·期 5 ·289 · IF 6.085

Fluorescent Labeling of Polymannuronic Acid and Its Distribution in Mice by Tail Vein Injection

Shuliang Song,Qiang Wei,Ke Wang,Qiong Yang,Yu Wang,Aiguo Ji,Guanjun Chen

Polymannuronic acid (PM) possesses more pharmacological activities than sodium alginate, but there have been few studies on its absorption mechanism, tissue distribution, and pharmacokinetics. Studies of pharmacokinetics and tissue distribution are necessary to elucidate the pharmacological effects of PM. Thus, we used fluorescein isothiocyanate (FITC) to produce fluorescently labeled PM (FITC-PM) and detected the distribution and pharmacokinetics of PM in vivo via tail vein injection. The results demonstrate that the FITC-PM showed high stability in different pH solutions. After the tail vein injection, FITC-PM tended to be distributed in the kidney, followed by the liver and in the heart, spleen, and lungs at lower concentrations. Pharmacokinetic analysis showed that the elimination rate constant of FITC-PM was 0.24, the half-life time was 2.85 h, the peak concentration was 235.17 μg/mL, the area under the curve was 631.48 μg/mL·h, the area under the curve by statistical moment was 1843.15 μg/mL·h2, the mean residence time was 2.92 h, and the clearance rate was 79.18 mL/h. These results indicate that FITC-PM could be used for PM distribution and pharmacokinetic studies, and the studies of pharmacokinetics and tissue distribution provided basic information that can be used to further clarify PM pharmacodynamic mechanisms.Keywords:polymannuronic acid;FITC;tissue distribution;pharmacokinetics;plasma concentration

研究领域: 生物化学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2022 · IF 3.571

Monitoring of salicylic acid content in human saliva and its relationship with plasma concentrations

Shengyu Cheng,Xianglin Xu,Xinxin Kong,Yudi Jiang,Luxuan Mo,Mingxia Li,Yueying Jin,Yu Han,Xi-Ling Li,Toufeng Jin,Jun Zhe Min

Aspirin is a widely used anti-inflammatory drug. It is reported that a relationship may exist between salicylic acid content in plasma and saliva after taking aspirin. This study established a rapid, convenient, and safe method to assess salicylic acid concentration in human saliva. A novel HPLC-ultraviolet detector was used to measure salicylic acid concentrations in human saliva and plasma. A C18 reversed-phase column with an aqueous solution of 0.1% trifluoroacetic acid (TFA)–acetonitrile mobile phase was used, and drug peaks were recorded at 303 nm. Salicylic acid was completely separated in saliva and plasma. Excellent linearity and correlation (r 2 ≥ 0.9999) was observed between 0.1 and 2.0 μg/mL. The detection limit (S/N = 3) was 33 ng/mL, and intra- and inter-day recoveries were 103.5–113.3% and 101.1–109.5%, respectively. Salicylic acid was measured within nine hours after administration of acetylsalicylic acid tablets. A positive correlation between salicylic acid content in saliva and plasma was found (r = 0.867, p  < 0.001). The proposed method was used successfully to measure salicylic acid concentration in human saliva. Meanwhile, we explored the relationship between salicylic acid levels in plasma and saliva. Saliva might replace blood for monitoring aspirin treatment. In addition, the research provides a reference for application to saliva samples.

CAS / MDL: 76-05-1
研究领域: 药理学 · 分析化学 · 临床化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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EUROPEAN FOOD RESEARCH AND TECHNOLOGY · 2025 · IF 3.2

Determination of seven fatty acids in plasma of rats after oral administration of Xanthoceras sorbifolia bunge oil by GC-MS and pharmacokinetic study

Guo Shuang,Qiao Xuan,Lv Zihan,Li Lintao,Liang Yutong,Meng Zhiyun,Gan Hui,Gu Ruolan,Wu Zhuona,Dou Guifang,Li Gaoying,Liu Shuchen

This work aims to establish a highly selective, sensitive, and accurate gas chromatography-mass spectrometry (GC-MS) method for detecting concentrations of seven representative fatty acids absorbed into the bloodstream after a single gavage of 10 mL/kg Xanthoceras sorbifolia Bunge ( X.sorbifolia ) oil in rats and conducting pharmacokinetic studies. The plasma samples were processed using two-step derivatization with NaOH and BF 3 -CH 3 OH, with an Agilent HP-88 capillary column serving as the stationary phase. Concentrations of seven fatty acids, namely hexadecanoic acid (palmitic acid, C16:0), octadecenoic acid (stearic acid, C18:0), cis -9-octadecenoic acid (oleic acid, C18:1), cis -9,12-octadecadienoic acid ( linoleic acid, C18:2), cis -11-eicosenoic acid (gondoic acid, C20:1), cis -13-docosaenoic acid (erucic acid, C22:1), and cis -15-tetracosenoic acid (nervonic acid, C24:1), were quantitatively determined under programmed temperature and ion detection mode. The results showed that the seven fatty acids were well separated and exhibited a good linear relationship between concentration and peak area ratio within the detection range (R 2  > 0.99). The precision and accuracy within and between batches were both less than 15%. After derivatization, the plasma samples remained stable at -20 °C, 4 °C, and 10 °C; The matrix effect did not affect the quantitative analysis, and the extraction recovery rate ranged from 100.3% to 107.76%. After gavage administration of X.sorbifolia oil to rats, the levels of unsaturated fatty acids in the blood were significantly increased compared to those in the blank control group. The peak concentration (T max) was 7–8 h, and the mean retention time (MRT) was 10–12 h. This experiment provides a basis for elucidating the potential material basis of the nutritional efficacy of X. sorbifolia oil after oral administration.

CAS / MDL: 112-63-0
研究领域: 分析化学 · 药理学 · 生物化学 · 营养学 · 药物化学
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Drug Design Development and Therapy · 2025 · IF 5.1

Simultaneous Determination of Unbound Plasma Concentration of Methotrexate and 7-Hydroxymethotrexate in Children Patients Receiving High-Dose Methotrexate Therapy

Wei-Chong Dong,Shuai-Shuai Gao,Bo Shi,Hao-Ran Li,Ye Jiang,Jia-Liang Guo,Zhi-Qing Zhang,Ying-Ze Zhang

Background High-dose methotrexate (HD-MTX) is seen as an effective therapy for acute lymphoblastic leukemia (ALL); however, it is extremely toxic. Monitoring the plasma concentrations of methotrexate (MTX) and its important metabolite, 7-hydroxy-methotrexate (7-OH-MTX), on a routine basis aids in dose modification of rescue medications and in avoiding toxicity. The pharmacologically active and toxic effects of drugs are due to the unbound portion, as most drugs are bound to plasma proteins to some degree. However, the simultaneous measurement of unbound plasma concentrations of MTX and 7-OH-MTX has not been reported.Methods We developed and validated a hollow fiber centrifugal ultrafiltration (HFCF-UF) technology to simultaneously analyze unbound MTX and 7-OH-MTX concentrations in human plasma. In total, 234 plasma samples from 58 children diagnosed with ALL who were administered HD-MTX were used in our study. We investigated the connection between unbound and total plasma concentrations of MTX and 7-OH-MTX, as well as how these concentrations relate to liver and renal function.Results The method that was developed is both simple and accurate. A weak linear relationship was observed between the concentrations of unbound and total 7-OH-MTX (r2 = 0.732). The concentration of total MTX and unbound 7-OH-MTX were both positively correlated with creatinine (Cr) levels and negatively correlated with Creatinine clearance (CCr). There was a wide variation in the concentration ratios of 7-OH-MTX to MTX, both total and unbound, and these ratios were significantly lower in individuals with impaired liver function.Conclusion The total concentration of 7-OH-MTX is an unreliable predictor of unbound concentration, necessitating the monitoring of unbound levels. The concentration ratios of 7-OH-MTX to MTX (both total and unbound) could be more accurate and sensitive biomarkers for predicting hepatotoxicity.

CAS / MDL: 64-18-6
研究领域: 药理学 · 肿瘤学 · 临床医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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