Journal of pharmaceutical and biomedical analysis最新文献_第2页

Development and validation of an analytical method for the simultaneous quantitation of posaconazole Form I and Form-S in oral suspensions 开发并验证同时定量口服混悬液中泊沙康唑 I 型和 S 型的分析方法。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2024-11-15 DOI: 10.1016/j.jpba.2024.116569

Michail Lykouras , Christos Kontoyannis , Malvina Orkoula

Any polymorphic conversion of an active pharmaceutical ingredient (API), even if partial, is likely to lead to changes in its efficiency and safety. Posaconazole, an antifungal drug, is detected as Form-S in the commercially available oral suspensions. However, a mixture of Form-S and the initial Form I is likely to coexist depending either on the manufacturing process of the suspensions and/or to the storage conditions of the suspension. The simultaneous quantitation of these crystal forms in suspensions is challenging because of the dose inhomogeneity and the instability of Form-S at ambient conditions. Although X-ray Powder Diffraction (XRPD) was initially employed, preferred orientation issues in the suspension inhibited the successful quantitative determination of the polymorphs. In order to circumvent the problem Raman spectroscopy was selected for addressing this challenge, while the additional application of a home-made rotation system reduced the inhomogeneity problems. A separate calibration curve was generated for each polymorph using a conventional linear regression. The combination of these two relations led to the formation of a comprehensive equation relating the characteristic Raman peak intensities of posaconazole Form-S and Form I with the concentrations thereof. The method was validated and the results were confirmed through a partial least square regression (PLSR). The detection limits for Form-S and Form I were determined equal to 1.9 mg/mL and 2.2 mg/mL, respectively.

活性药物成分（API）的任何多态转化，即使是部分转化，都有可能导致其效率和安全性发生变化。泊沙康唑（Posaconazole）是一种抗真菌药物，在市售口服混悬液中检测到的是 Form-S。然而，由于悬浮剂的生产工艺和/或悬浮剂的储存条件不同，S 型和 I 型的混合物很可能同时存在。由于剂量的不均匀性和 Form-S 在环境条件下的不稳定性，同时对悬浮液中的这些晶体形态进行定量具有挑战性。虽然最初采用了 X 射线粉末衍射 (XRPD)，但悬浮液中的优先取向问题阻碍了多晶型的成功定量测定。为了规避这一问题，我们选择了拉曼光谱来解决这一难题，同时额外应用自制的旋转系统来减少不均匀性问题。使用传统的线性回归方法为每种多晶型生成了单独的校准曲线。将这两种关系结合起来，就形成了泊沙康唑 Form-S 和 Form I 的特征拉曼峰强度与浓度之间的综合方程。通过偏最小二乘法回归（PLSR）对该方法进行了验证并确认了结果。经测定，Form-S 和 Form I 的检出限分别为 1.9 mg/mL 和 2.2 mg/mL。

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引用次数: 0

Probe electrospray ionization coupled to a quadrupole time-Of-flight: A feasibility study for the detection of cocaine and its derivatives in oral fluid 探针电喷雾离子化与四极杆飞行时间相结合：检测口腔液中可卡因及其衍生物的可行性研究。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2024-11-15 DOI: 10.1016/j.jpba.2024.116568

Elisa Jousselin , Elies Zarrouk , Pauline Griffeuille , Sylvain Dulaurent , Souleiman El Balkhi , Franck Saint-Marcoux

Probe Electrospray Ionization (PESI) is an atmospheric pressure ionization method that can be directly coupled with a mass spectrometer to allow ultrafast analyses without chromatographic separation and with minimal sample preparation. Using the particular case of cocaine and its metabolites in human oral fluid, the main objective of the present study was to test the feasibility of a new hybrid system combining a PESI source and a quadrupole time-of-flight (QTOF). The best results were obtained for a sample preparation with a simple dilution of 100 µL of oral fluids in an ethanol / 10 mM ammonium formate buffer (50/50) and 10 µL deposited on a dedicated sample plate and introduced into the PESI source. For HRMS acquisition, an approach consisting in a full-mass scan (“untargeted approach” from 100 to 500 m/z; MS1) followed by a targeted scheduled MSMS acquisition (precursor ions of the 3 molecules of interest and their 3 internal standards; MS2) gave the best signals. The total time of analysis was 0.45 min and the method was validated according to ISO15189 standard for a 5–100 ng/mL range, including accuracy and precision (inter-day and intra-day precision and bias values were lower than 15 %), matrix effect, carryover and specificity (no interference with a mixture of 119 psychotropic drugs spiked at 1 mg/L). The LLOD values were 1 ng/mL for the 3 cocaine derivatives and 83 Driving Under the Influence of Drug (DUID) cases sent to our Lab for the determination of illicit drugs in oral fluid were analyzed using the PESI-QTOF method and compared to a LC-MS/MS method. A perfect agreement was observed between the 2 methods, whether the cases were positive or negative. Cocaine was detected in 51 out of these 83 real cases (61.6 %). BZE and EME were also simultaneously detected in 50 of them (98.5 %). This feasibility study reports the first analytical method based on a coupling of a PESI source to a QTOF mass spectrometer. Adding the major advantage of high specificity through HRMS is a step forward for PESI technology.

探针电喷雾离子化（PESI）是一种常压离子化方法，可直接与质谱仪联用，无需色谱分离，只需进行最少的样品制备即可进行超快速分析。本研究以人体口腔液中的可卡因及其代谢物为例，主要目的是测试将 PESI 源和四极杆飞行时间（QTOF）相结合的新型混合系统的可行性。样品制备的最佳结果是将 100 µL 口腔液在乙醇/10 mM 甲酸铵缓冲液（50/50）中进行简单稀释，然后将 10 µL 沉积在专用样品板上并导入 PESI 源。对于 HRMS 采集，先进行全质量扫描（从 100 m/z 到 500 m/z 的 "非目标方法"；MS1），然后再进行目标预定 MSMS 采集（3 个相关分子的前体离子及其 3 个内部标准；MS2），这样可以获得最佳信号。该方法的准确度和精密度（日间和日内精密度和偏差值均低于 15%）、基质效应、携带和特异性（在 119 种精神药物的混合物中以 1 mg/L 加标时无干扰）均符合 ISO15189 标准。使用 PESI-QTOF 方法分析了送往本实验室检测口服液中非法药物含量的 83 个受毒品影响驾驶（DUID）案例，并与 LC-MS/MS 方法进行了比较。无论是阳性还是阴性病例，两种方法的结果都完全一致。在这 83 个真实样本中，有 51 个样本（61.6%）检测出了可卡因。其中 50 例（98.5%）同时检测出 BZE 和 EME。本可行性研究报告首次提出了基于 PESI 源与 QTOF 质谱仪耦合的分析方法。通过 HRMS 增加高特异性的主要优势是 PESI 技术向前迈出的一步。

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引用次数: 0

Portable Raman spectroscopy and fourier transform near infrared spectroscopy for the quantification of different sinomenine hydrochloride crystal forms 用便携式拉曼光谱和傅立叶变换近红外光谱定量分析盐酸西诺明的不同晶型。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2024-11-14 DOI: 10.1016/j.jpba.2024.116567

Zehua Ying , Zixuan Yan , Xuting Guo , Cunhao Li , Guoxiang Li , Xingli He , Wenlong Li

The objective of this paper is to rapidly and accurately quantify the content of the dominant crystal form of Sinomenine hydrochloride (SH) and to evaluate the respective characteristics of Raman spectroscopy and Fourier transform near infrared spectroscopy techniques for rapid quantification of crystalline substances. In this study, we performed an adulterated gradient quantification based on two new crystalline forms of SH prepared in the laboratory in combination with commercially available products. And established 86 samples containing 66 batches of ternary and 20 batches of binary mixtures. We quantified SH possessing polycrystalline forms based on two kinds of spectroscopy techniques combined with chemometric methods. In the process of establishing the partial least squares quantitative model, according to the experimental design thought, we used the ensemble preprocessing method to screen the optimal preprocessing method for the spectral data of crystal samples. Then we optimized four variable selection methods by single factor investigation. Finally, after completing the PLSR model, we found that the regression models established for both Raman spectra (RMSEP = 0.00672) and FT-NIR spectra (RMSEP = 0.00533) have a high ability to rapidly quantify the crystals.

本文旨在快速准确地量化盐酸西诺明（SH）主要晶型的含量，并评估拉曼光谱和傅立叶变换近红外光谱技术在快速量化结晶物质方面的各自特点。在这项研究中，我们基于实验室制备的两种新的盐酸西诺明结晶形式，结合市售产品进行了掺假梯度定量。共建立了 86 个样品，其中包括 66 批三元混合物和 20 批二元混合物。我们根据两种光谱技术结合化学计量学方法对多晶体 SH 进行了定量分析。在建立偏最小二乘法定量模型的过程中，根据实验设计思想，采用集合预处理方法筛选出晶体样品光谱数据的最优预处理方法。然后通过单因素考察优化了四种变量选择方法。最后，在完成 PLSR 模型后，我们发现拉曼光谱（RMSEP = 0.00672）和傅立叶变换近红外光谱（RMSEP = 0.00533）所建立的回归模型都具有较高的快速量化晶体的能力。

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引用次数: 0

Brewer’s spent grain as a potential sorbent for toxicology methods: Application to antidepressant analysis in urine 啤酒糟作为毒理学方法的潜在吸附剂：应用于尿液中抗抑郁剂的分析。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2024-11-13 DOI: 10.1016/j.jpba.2024.116564

Letícia Birk , Bruno Pereira dos Santos , Daniela Souza Ossanes , Patrícia de Souza Schwarz , Suyanne Angie Lunelli Bachmann , Viviane Cristina Sebben , Sarah Eller , Tiago Franco de Oliveira

The use of antidepressants is well-documented for several health conditions. The determination of these drugs in biological fluids is often important in intoxication cases. However, appropriate sample preparation needs to be employed, such as dispersive liquid phase microextraction (DSPME). Therefore, this study aimed to develop a method for the determination of antidepressants in urine using Brewer’s spent grain (BSG) as sorbent in a DSPME procedure, followed by GC-MS analysis. In this methodology, only 500 µL of urine was required, alongside 15 mg of BSG as the sorbent for the DSPME technique. Desorption step was performed with 500 µL of ethyl acetate:MTBE solution (1:1, v/v), followed by evaporation of the organic layer, reconstitution in acetonitrile and injection into the analytical system. BSG was further characterized by several analytical techniques. The DSPME procedure was optimized using multivariate strategies, and the method was fully validated according to proper guidelines. Lower limits of quantitation (LLOQ) were set between 50 and 200 ng/mL, while linearity was achieved over the specified range of LLOQ to 5000 ng/mL, with R² ≥ 0.99. Additionally, the method was applied to the analyses of 109 urine samples. Of these, 76 were positive for at least one antidepressant, with the most prevalent being nortriptyline, amitriptyline, and fluoxetine. This study is the first to report the use of BSG as a sorbent for DSPME, demonstrating good efficiency as indicated by the analytical figures of merit. Moreover, the method proved to be applicable in real poisoning case samples. The analytical performance, combined with advantages such as high throughput and a green profile, suggests this method as a valuable alternative for toxicological laboratories.

抗抑郁药被广泛用于治疗多种疾病。在中毒事件中，生物液体中这些药物的检测往往非常重要。然而，需要采用适当的样品制备方法，如分散液相微萃取（DSPME）。因此，本研究旨在开发一种测定尿液中抗抑郁药物的方法，在 DSPME 程序中使用布鲁尔废谷物（BSG）作为吸附剂，然后进行 GC-MS 分析。在该方法中，只需 500 µL 尿液和 15 毫克 BSG 作为 DSPME 技术的吸附剂。解吸步骤使用 500 µL 乙酸乙酯：MTBE 溶液（1:1，v/v）进行，然后蒸发有机层，在乙腈中重组，并注入分析系统。几种分析技术对 BSG 进行了进一步表征。采用多元策略对 DSPME 程序进行了优化，并根据适当的指南对该方法进行了全面验证。定量下限（LLOQ）设定为 50 至 200 ng/mL，线性范围为 LLOQ 至 5000 ng/mL，R2 ≥ 0.99。此外，该方法还用于分析 109 份尿样。其中 76 份尿样中至少有一种抗抑郁药呈阳性，最常见的是去甲替林、阿米替林和氟西汀。该研究首次报道了使用 BSG 作为 DSPME 的吸附剂，其分析结果表明该方法具有良好的效率。此外，该方法还被证明适用于真实的中毒案例样本。分析性能加上高通量和绿色环保等优势，表明该方法是毒理学实验室的一种有价值的替代方法。

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引用次数: 0

Dual-mode, signal-amplified DNA biosensor for label-free, reliable assay of gestational diabetes mellitus-related miRNA (miR-135a) 用于无标记、可靠检测妊娠糖尿病相关 miRNA (miR-135a)的双模式、信号放大 DNA 生物传感器。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2024-11-12 DOI: 10.1016/j.jpba.2024.116565

Jiang-Nan Zhang, Feng-Min Liu, Xiao-Juan Du, Xi-Le Zhao

miR-135a is highly expressed in patients with gestational diabetes mellitus, and its target genes are also involved in insulin signaling pathway, so it is one biomarker for gestational diabetes mellitus. Herein we designed a dual-mode DNA biosensor for reliable assay of miR-135a based on the fluorescence and colorimetric signals. Several experiments were carried out to demonstrate the assay feasibility and mechanism for this dual-mode DNA biosensor. With optimum parameters, this proposed dual-mode biosensor has been realized sensitive and quantitative assay of miR-135a. For the fluorescence and colorimetric signals, the working ranges are 0.56–61 and 8.3–74 nM, while limits of detection are 0.18 and 3.7 nM respectively. This dual-mode strategy allows two independent signals for miR-135a assay, so it can verify each other to show more accurate results with good fidelity. Furthermore, there is a good selectivity in the biosensor for target miR-135a over other nucleotide variants, as well as good anti-interference ability in complex samples. This dual-mode DNA biosensor provides a new approach for miR-135a assay and miRNA expression profiling in gestational diabetes mellitus.

miR-135a 在妊娠糖尿病患者中高表达，其靶基因也参与了胰岛素信号通路，因此是妊娠糖尿病的生物标志物之一。在此，我们设计了一种基于荧光和比色信号的双模式 DNA 生物传感器，用于可靠地检测 miR-135a。为了证明这种双模式 DNA 生物传感器的检测可行性和机制，我们进行了多项实验。通过优化参数，该双模式生物传感器实现了对 miR-135a 的灵敏定量检测。荧光信号和比色信号的工作范围分别为 0.56-61 nM 和 8.3-74 nM，检测限分别为 0.18 nM 和 3.7 nM。这种双模式策略使 miR-135a 检测具有两个独立的信号，因此可以相互验证，从而显示出更准确、更可靠的结果。此外，该生物传感器对目标 miR-135a 而不是其他核苷酸变体具有良好的选择性，在复杂样品中也具有良好的抗干扰能力。这种双模式 DNA 生物传感器为妊娠糖尿病的 miR-135a 检测和 miRNA 表达谱分析提供了一种新方法。

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引用次数: 0

GC-MS uncovers unique metabolic markers of drug-resistant epilepsy in capillary but not venous dried blood spots GC-MS 在毛细血管而非静脉干血斑中发现了耐药性癫痫的独特代谢标记物。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2024-11-04 DOI: 10.1016/j.jpba.2024.116561

Sing Teang Kong , Shih-Hui Lim , Jianhong Ching , Paul Chi-Lui Ho

This study compared the effectiveness of capillary dried blood spots (DBS) versus venous DBS in detecting metabolic changes related to drug-resistant epilepsy (DRE). DBS samples were collected from 142 epilepsy patients (58 drug-resistant, 84 drug-responsive) via venipuncture or fingerstick capillary sampling. Metabolomic analysis using gas chromatography-mass spectrometry compared DBS metabolite profiles between the two groups. While venous DBS profiles showed no distinct patterns, capillary DBS profiles revealed clustering patterns in principal components analysis, with the first two principal components explaining 14.5 %, and 13.5 % of the total variance, respectively. Orthogonal PLS-DA confirmed group discrimination (R2Y=0.989, Q2=0.742). Drug-resistant patients exhibited elevated capillary DBS levels of glutamine, pyruvic acid, and serine, and decreased palmitic acid compared to drug-responsive patients. Pathway analysis revealed disruptions in amino acid metabolism, neurotransmission, and cellular energy regulation. Elevated glutamine levels may contribute to an imbalance between excitatory glutamate and inhibitory GABA neurotransmission, key factors in epileptogenesis and drug resistance. Capillary DBS, likely enriched with arterial blood supply to the brain, appears to better capture central nervous system metabolic disturbances compared to venous DBS containing systemic contributions. This minimally invasive capillary DBS approach offers effective metabolic profiling of brain conditions like DRE, for monitoring disease progression and treatment response, enhancing personalized patient management in epilepsy.

这项研究比较了毛细血管干血斑（DBS）与静脉 DBS 在检测与耐药性癫痫（DRE）相关的代谢变化方面的有效性。研究人员通过静脉穿刺或毛细管指针采样采集了 142 名癫痫患者（58 名耐药患者和 84 名药物反应性患者）的干血细胞样本。利用气相色谱-质谱法进行代谢组学分析，比较了两组患者的 DBS 代谢物谱。静脉 DBS 图谱没有显示出明显的模式，而毛细管 DBS 图谱在主成分分析中显示出聚类模式，前两个主成分分别解释了总方差的 14.5% 和 13.5%。正交 PLS-DA 证实了组别区分（R2Y=0.989，Q2=0.742）。与药物反应患者相比，耐药患者的毛细血管 DBS 中谷氨酰胺、丙酮酸和丝氨酸水平升高，棕榈酸水平降低。通路分析显示，氨基酸代谢、神经传递和细胞能量调节发生了紊乱。谷氨酰胺水平升高可能导致兴奋性谷氨酸和抑制性GABA神经传递失衡，而这正是癫痫发生和耐药性的关键因素。毛细血管 DBS 可能富含大脑动脉供血，与含有全身供血的静脉 DBS 相比，毛细血管 DBS 似乎能更好地捕捉到中枢神经系统的代谢紊乱。这种微创的毛细血管 DBS 方法能有效地分析 DRE 等脑部疾病的代谢情况，用于监测疾病进展和治疗反应，从而加强癫痫患者的个性化管理。

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引用次数: 0

Evaluation of protein impurities in Ademetionine 1,4-Butanedisulfonate 评估 1,4-丁二磺酸阿德米汀宁中的蛋白质杂质。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2024-11-04 DOI: 10.1016/j.jpba.2024.116560

Yangrui Zhang , Xintong Jiang , Fengting Ou , Chen Guo , Qin Ye , Lushan Yu

Ademetionine 1,4-Butanedisulfonate (SAMe) is widely used as a prescription drug to treat cholestasis associated with liver disease, and is also used to treat depression, Alzheimer's disease and other diseases. Currently, the main way to produce SAMe is by fermentation of S-adenosylmethionine synthetase（SAMS）. However, during the fermentation process, host cells produce contaminants unrelated to the treatment. Among them, host cell protein (HCP), which is co-purified with the drug, is the main impurity in the production process. HCP-induced antigenic reactions can lead to allergies or other adverse reactions and affect drug quality, efficacy, and safety. Enzyme-linked immunosorbent assay (ELISA) and mass spectrometry (MS) are currently used as the main analytical methods for measuring HCP. The ELISA method may ignore some HCPs with low immunogenicity, while mass spectrometry is primarily employed for the characterization of proteomes. Orthogonal methods can more effectively evaluate impurities in drugs. In this study, ELISA was initially utilized to quantify the content of Saccharomyces cerevisiae host protein in 11 batches of SAMe active pharmaceutical ingredient (API) from two suppliers, then the above APIs were qualitatively analyzed by MS method. Following the identification of surrogate peptide of SAMS, an Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry（UPLC-MS/MS）method was established and validated, the SAMS protein residues in 11 batches of samples were subsequently determined. The results demonstrated that the levels of Saccharomyces cerevisiae host protein and SAMS in the samples were both low, with values below 20 ppm and 1.19 ppm, respectively. The qualitative results also indicate that the types of peptide residues in the samples are more diverse than those of protein residues. Furthermore, residues of proteins and peptides can be detected in all samples, which underscores the importance of evaluating the HCP in API. This study employs a range of complementary detection methods to conduct a comprehensive and sensitive evaluation of total HCP and specific proteins in drugs, thereby guiding more informed assessments of the risks posed by HCP impurities in raw materials during pharmaceutical processes.

腺苷蛋氨酸 1,4-丁二磺酸盐（SAMe）作为一种处方药被广泛用于治疗与肝病有关的胆汁淤积症，还可用于治疗抑郁症、老年痴呆症和其他疾病。目前，生产 SAMe 的主要方法是 S-腺苷蛋氨酸合成酶（SAMS）发酵法。然而，在发酵过程中，宿主细胞会产生与处理无关的污染物。其中，与药物共同纯化的宿主细胞蛋白（HCP）是生产过程中的主要杂质。HCP 引起的抗原反应会导致过敏或其他不良反应，影响药物的质量、疗效和安全性。酶联免疫吸附法（ELISA）和质谱法（MS）是目前测量 HCP 的主要分析方法。酶联免疫吸附法可能会忽略一些免疫原性低的 HCP，而质谱法主要用于表征蛋白质组。正交方法能更有效地评估药物中的杂质。本研究首先利用酶联免疫吸附法对两家供应商提供的 11 批 SAMe 原料药中的酵母宿主蛋白含量进行了定量分析，然后利用质谱法对上述原料药进行了定性分析。在鉴定出SAMS的替代肽后，建立并验证了超高效液相色谱-串联质谱（UPLC-MS/MS）方法，随后测定了11批次样品中SAMS蛋白的残留量。结果表明，样品中的酿酒酵母宿主蛋白和 SAMS 含量都很低，分别低于 20 ppm 和 1.19 ppm。定性结果还表明，与蛋白质残基相比，样品中的肽残基类型更为多样。此外，所有样品中都能检测到蛋白质和肽的残留物，这突出了评估原料药中 HCP 的重要性。本研究采用了一系列互补检测方法，对药物中的总 HCP 和特定蛋白质进行了全面而灵敏的评估，从而指导对制药过程中原料中 HCP 杂质带来的风险进行更明智的评估。

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引用次数: 0

Identification of a novel vardenafil analogue, 19-O-propyl hydroxy vardenafil, as a dietary supplement adulterant 鉴定新型伐地那非类似物19-O-丙基羟基伐地那非为膳食补充剂掺假物。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2024-11-04 DOI: 10.1016/j.jpba.2024.116563

Hui-Chun Lee , You-Lun Wu , Yu-Ting Lin , Li-Yao Tsai , Ya-Min Kao , Mei-Chih Lin , Su-Hsiang Tseng

A novel vardenafil analogue was discovered during adulterant screening of a dietary supplement. After extraction and purification, this analogue was identified using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) analyses. The molecular formula determined using LC-HRMS was C₂₄H₃₄N₆O₅S. Fragmentation data suggested that this unknown compound may have two modifications to vardenafil. NMR analysis confirmed the presence of a hydroxyl group on the piperazine moiety and a propyl group attached to the phenoxy group. Consequently, this compound was named 19-O-propyl hydroxy vardenafil.

在对一种膳食补充剂进行掺假筛选时发现了一种新型伐地那非类似物。经过提取和纯化，利用液相色谱-高分辨质谱（LC-HRMS）和核磁共振（NMR）分析鉴定出了这种类似物。液相色谱-高分辨质谱（LC-HRMS）测定的分子式为 C24H34N6O5S。碎片数据表明，这种未知化合物可能对伐地那非进行了两种修饰。核磁共振分析证实，哌嗪分子上有一个羟基，苯氧基上有一个丙基。因此，这种化合物被命名为 19-O-丙基羟基伐地那非。

引用次数: 0

GC-MS and multivariate analysis reveal partial serum metabolome restoration by bevacizumab in a colon cancer rat model: An untargeted metabolomics investigation GC-MS 和多元分析揭示了贝伐珠单抗对结肠癌大鼠模型血清代谢组的部分修复作用：非靶向代谢组学研究。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2024-11-04 DOI: 10.1016/j.jpba.2024.116562

Maram H. Abduljabbar , Yusuf S. Althobaiti , Reem M. Alnemari , Farooq M. Almutairi , Muneef M. Aldhafeeri , Ahmed Serag , Atiah H. Almalki

Bevacizumab is an anti-angiogenic therapeutic agent that targets vascular endothelial growth factor (VEGF) and has been approved for the treatment of several types of cancer, including colon cancer. Herein, a GC-MS based metabolomics approach was employed to investigate the impact of bevacizumab on the serum metabolome of colon cancer rats. Multivariate chemometric analysis models such as PCA and PLS-DA showed a clear separation between the control, cancer and bevacizumab-treated groups, suggesting that bevacizumab administration induced significant metabolic alterations. Furthermore, pairwise comparisons between the studied groups using the OPLS-DA model in addition to univariate analysis identified several discriminatory metabolites belonged to various chemical classes including amino acids, organic acids and fatty acids that were perturbed between the studied groups. Interestingly, bevacizumab treatment was able to partially restore some of the cancer-induced metabolic disturbances, indicating its potential therapeutic efficacy via improving the tumor vasculature and nutrient delivery. Besides, pathway analysis of the differential metabolites identified key metabolic pathways affected by bevacizumab, which included valine, leucine and isoleucine metabolism, pyruvate metabolism and butanoate metabolism. However, little effects were observed on lipid metabolites such as palmitic acid and stearic acid and consequently their related metabolic pathways such as fatty acid biosynthesis metabolism suggesting that bevacizumab has more prominent effect on energy and amino acid metabolisms as compared to fatty acid metabolism in colon cancer rats. Overall, our study provided novel insights into the metabolic mechanisms underlying the therapeutic effects of bevacizumab in colon cancer rats via the use of a comprehensive GC-MS metabolomics approach.

贝伐珠单抗是一种针对血管内皮生长因子（VEGF）的抗血管生成治疗药物，已被批准用于治疗包括结肠癌在内的多种癌症。本文采用基于 GC-MS 的代谢组学方法研究贝伐珠单抗对结肠癌大鼠血清代谢组的影响。PCA和PLS-DA等多元化学计量分析模型显示，对照组、癌症组和贝伐珠单抗治疗组之间存在明显的差异，这表明贝伐珠单抗会诱发显著的代谢改变。此外，除了单变量分析之外，还利用 OPLS-DA 模型对研究组进行了配对比较，确定了研究组之间存在干扰的几种具有鉴别性的代谢物，它们属于不同的化学类别，包括氨基酸、有机酸和脂肪酸。有趣的是，贝伐珠单抗治疗能够部分恢复癌症引起的代谢紊乱，这表明贝伐珠单抗通过改善肿瘤血管和营养输送具有潜在疗效。此外，对不同代谢物的通路分析发现了贝伐单抗影响的关键代谢通路，包括缬氨酸、亮氨酸和异亮氨酸代谢、丙酮酸代谢和丁酸代谢。然而，我们几乎没有观察到贝伐珠单抗对棕榈酸和硬脂酸等脂质代谢物及其相关代谢途径（如脂肪酸生物合成代谢）的影响，这表明与脂肪酸代谢相比，贝伐珠单抗对结肠癌大鼠能量和氨基酸代谢的影响更为突出。总之，我们的研究通过使用全面的 GC-MS 代谢组学方法，为了解贝伐珠单抗对结肠癌大鼠治疗作用的代谢机制提供了新的见解。

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引用次数: 0

Combination of plasma-based lipidomics and machine learning provides a useful diagnostic tool for ovarian cancer 基于血浆的脂质组学与机器学习相结合，为卵巢癌的诊断提供了有用的工具。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2024-11-02 DOI: 10.1016/j.jpba.2024.116559

Jinhua Rong , Guojun Sun , Jing Zhu , Yiming Zhu , Zhongjian Chen

Ovarian cancer (OC), the second leading cause of death among gynecological cancers, is often diagnosed at an advanced stage due to its asymptomatic nature at early stages. This study aimed to explore the diagnostic potential of plasma-based lipidomics combined with machine learning (ML) in OC. Non-targeted lipidomics analysis was conducted on plasma samples from participants with epithelial ovarian cancer (EOC), benign ovarian tumor (BOT), and healthy control (HC). The samples were randomly divided into a train set and a test set. Differential lipids between groups were selected using two-tailed Student’s t-test and partial least squares discriminant analysis (PLS-DA). Both single lipid-based receiver operating characteristic (ROC) model, and multiple lipid-based ML model, were constructed to investigate the diagnostic value of the differential lipids. The results showed several lipids with significant diagnostic potential. ST 27:2;O achieved the highest prediction accuracy of 0.92 in distinguishing EOC from HC. DG 42:2 had the highest prediction accuracy of 0.96 in diagnosing BOT from HC. Cer d18:1/18:0 had the highest prediction accuracy of 0.65 in differentiating EOC from BOT. Furthermore, multiple lipid-based ML models illustrated better diagnostic performance. K-nearest neighbors (k-NN), partial least squares (PLS), and random forest (RF) models achieved the highest prediction accuracy of 0.96 in discriminating EOC from HC. The support vector machine (SVM) model reached the highest prediction accuracy both in distinguishing BOT from HC, and in differentiating EOC from BOT, with accuracies of 1.00 and 0.74, respectively. In conclusion, this study revealed that the combination of plasma-based lipidomics and ML algorithms is an effective method for diagnosing OC.

卵巢癌（OC）是妇科癌症中的第二大死因，由于其早期无症状，通常在晚期才被诊断出来。本研究旨在探索基于血浆的脂质组学与机器学习（ML）相结合对卵巢癌的诊断潜力。研究人员对上皮性卵巢癌（EOC）、良性卵巢肿瘤（BOT）和健康对照（HC）患者的血浆样本进行了非靶向脂质组学分析。样本被随机分为训练集和测试集。采用双尾学生 t 检验和偏最小二乘法判别分析（PLS-DA）选出组间差异脂质。建立了基于单一脂质的接收者操作特征（ROC）模型和基于多种脂质的 ML 模型，以研究差异脂质的诊断价值。结果显示，几种血脂具有显著的诊断潜力。ST 27:2;O 在区分 EOC 和 HC 方面的预测准确率最高，达到 0.92。在诊断 BOT 和 HC 时，DG 42:2 的预测准确率最高，达到 0.96。Cer d18:1/18:0 在区分 EOC 和 BOT 方面的预测准确率最高，为 0.65。此外，多个基于脂质的 ML 模型显示出更好的诊断性能。K-近邻（k-NN）、偏最小二乘（PLS）和随机森林（RF）模型在区分 EOC 和 HC 方面的预测准确率最高，达到 0.96。支持向量机（SVM）模型在区分 BOT 和 HC 以及区分 EOC 和 BOT 方面的预测准确率最高，分别为 1.00 和 0.74。总之，本研究揭示了基于血浆的脂质组学和 ML 算法相结合是诊断 OC 的有效方法。

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