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超高效合相色谱串联四极杆飞行时间质谱在司盘组成分析方法中的应用研究

李樾, 许凯, 杨锐, 杨会英

李樾,许凯,杨锐,等. 超高效合相色谱串联四极杆飞行时间质谱在司盘组成分析方法中的应用研究[J]. 中国药科大学学报,2024,55(6):742 − 749. DOI: 10.11665/j.issn.1000-5048.2024010502
引用本文: 李樾,许凯,杨锐,等. 超高效合相色谱串联四极杆飞行时间质谱在司盘组成分析方法中的应用研究[J]. 中国药科大学学报,2024,55(6):742 − 749. DOI: 10.11665/j.issn.1000-5048.2024010502
LI Yue, XU Kai, YANG Rui, et al. Application of ultra-high performance convergence chromatography-tandem quadrupole time-of-flight mass spectrometry in the analysis of Span composition[J]. J China Pharm Univ, 2024, 55(6): 742 − 749. DOI: 10.11665/j.issn.1000-5048.2024010502
Citation: LI Yue, XU Kai, YANG Rui, et al. Application of ultra-high performance convergence chromatography-tandem quadrupole time-of-flight mass spectrometry in the analysis of Span composition[J]. J China Pharm Univ, 2024, 55(6): 742 − 749. DOI: 10.11665/j.issn.1000-5048.2024010502

超高效合相色谱串联四极杆飞行时间质谱在司盘组成分析方法中的应用研究

详细信息
    通讯作者:

    杨锐: Tel:010-67095720 E-mail:yangr@nifdc.org.cn

    杨会英: Tel:010-53852486 E-mail:yanghuiying@nifdc.org.cn

  • 中图分类号: R917

Application of ultra-high performance convergence chromatography-tandem quadrupole time-of-flight mass spectrometry in the analysis of Span composition

  • 摘要:

    采用超高效合相色谱串联四极杆飞行时间质谱(UPCC-QTOF-MS)检测方法,建立定性分析药用辅料司盘组成的方法。采用VIRIDIS HSS C18 SB 100A 色谱柱 (3.0 mm×150 mm,18 μm),以CO2和异丙醇-四氢呋喃(98∶5)为流动相,梯度洗脱,柱温为50 ℃,流速为1 mL/min,以异丙醇-0.1%甲酸水溶液(8∶2)为补偿溶剂,背压为13.78 MPa,离子化模式为ESI+,采集模式为MSE,扫描范围m/z 100~1200,分别测定司盘20、40、60、80、85样品。 建立的方法可区分不同牌号司盘间组成差异,对各司盘组分进行定性分析,其中司盘20可分析得到21种组分,司盘40可分析得到7种组分,司盘60可分析得到13种组分,司盘80可分析得到9种组分,司盘85可分析得到9种组分,并根据各组分质谱图开展了结构分析。本研究建立的方法可区分不同牌号司盘间的组成差异,同时也可用于分析不同牌号的司盘组成及结构,此方法绿色环保,对司盘质量控制、工艺评价、制剂应用选择等具有指导意义。

    Abstract:

    A method for the qualitative analysis of the composition of pharmaceutical excipient Span was established by ultra-high performance convergence chromatography-tandem quadrupole time-of-flight mass spectrometry (UPCC-QTOF-MS). The separation was performed on a VIRIDIS HSS C18 SB 100A column (3.0 mm×150 mm, 18 μm) with gradient elution using CO2 and isopropanol-tetrahydrofuran (98∶5) as the mobile phase. The column temperature was 50 °C. The flow rate was 1 mL/min. Isopropanol and 0.1 % formic acid aqueous solution (8∶2) were used as the compensation solvent. The back pressure was 13.78 MPa. The ionization mode was ESI +, the acquisition mode was MSE, and the m/z scanning range was from 100 to 1200. The samples of Span 20, 40, 60, 80 and 85 were determined respectively. The established method could distinguish the composition differences between different brands of Span, and it could analyze the components of different brands of Span as well. 21 components could be analyzed by Span 20, 7 by Span 40, 13 by Span 60, 9 by Span 80, and 9 by Span 85, and the structural analysis of each component was carried out. The method established in this paper can distinguish the composition differences between different brands of Span. It can also be used to analyze the composition and structure of different brands of Span. This method is green and environmentally friendly with guiding significance for Span quality control, process evaluation, and preparation application selection, etc.

  • 口腔溃疡是一种临床上比较常见的口腔黏膜病变[1],引起局部剧烈疼痛[23]。虽然大多数口腔溃疡具有自限性[4],但复发率很高,严重时会影响患者的正常生活[5]。因此,促进口腔溃疡修复制剂的开发,具有重要的临床应用意义。

    研究表明,口腔溃疡与细菌感染有一定关系[68],碘单质能够直接卤化菌体蛋白质、杀死细菌、缓解伤口疼痛,因而用于口腔溃疡等疾病的治疗[9]。目前用于口腔溃疡治疗的碘制剂,主要有碘甘油和西地碘含片[10],可通过杀灭口腔中的细菌,消除溃疡面周围淤肿,起到杀菌、止痛、促进口腔溃疡修复的效果。但常规碘制剂在口腔中作用时间短、不能对溃疡部位有效保护,影响了其疗效的发挥。因此开发具有黏附作用及创面保护效果的新型的复方碘制剂,具有重要的研究意义和应用价值。

    凝胶剂具有良好的生物相容性和黏附性,并具有缓释作用[7, 1112],可延长药物在患处的作用时间,是目前口腔黏膜制剂的开发热点[13]。但凝胶剂在使用中存在不方便根据创面形状和大小调整,异物感较强,不易操作等问题。原位凝胶是以溶液状态给药后,能在用药部位快速发生相转变,由液态转化形成半固体凝胶的制剂,具有使用方便,可灵活调整大小形状的优势[14]

    本研究基于原位凝胶技术,设计开发了喷雾原位膜剂,具有成膜快,厚度薄的优势,更有利于口腔黏膜使用。基于该技术,制备的复方碘口腔喷雾原位膜,药液呈雾状喷出,在口腔溃疡创面形成原位膜,不仅对创面形成保护作用,并具有缓释效果,延长药物作用时间。本研究对聚丙烯酸树脂、海藻酸、羧甲基纤维素钠等为成膜材料进行筛选,并通过处方优化,制备了新型复方碘口腔喷雾原位膜,进一步对药液及原位膜的理化性质、体外释放、生物相容性及促口腔溃疡修复效果进行了体外及体内评价。该研究拓展了复方碘制剂在口腔溃疡治疗中的研究和应用,为新型口腔膜剂的设计和开发提供了新思路。

    海藻酸钠、氯化钙、冰醋酸(国药集团化学试剂有限公司);聚丙烯酸树脂L-100(Eudragit L-100 德国Evonik公司);羧甲基纤维素钠(CMC-Na,上海源叶生物科技有限公司);甘油(西陇科学股份有限公司);乌来糖(南京都莱生物技术有限公司);其他试剂均为市售分析纯。

    新西兰兔,雄性,3~4月龄,体重(2 ± 0.2) kg,合格证号:SYXK(苏)2023-0080;江苏大学动物中心提供。小鼠胚胎成纤维细胞3T6-Swiss albino购自中国科学院细胞库。所有动物实验均符合动物伦理委员会标准。

    DF-101S集热式恒温加热磁力搅拌器(巩义市创远仪器制造有限公司); TU-1901紫外可见分光光度计(北京普析通用仪器有限公司);800 TS酶标仪(南京必翔生物科技有限公司);ECLIPSE Ti倒置光显微镜(日本尼康公司)。

    称取碘化钾0.5 g,溶解于少量纯化水中,再加入碘0.2 g,配制复方碘溶液。分别称取一定量Eudragit L-100、CaCl2,加入乙醇100 mL,搅拌溶解,置于喷瓶中,即为药液A;称取一定量海藻酸钠、CMC-Na和增塑剂甘油,并加入配制好的复方碘溶液,加入纯水100 mL溶解,置于喷瓶中即为药液B。

    分别考察成膜材料Eudragit L-100 (25,37.5,50,62.5 mg/mL)、氯化钙 (2.5,5 ,7.5 ,10 mg/mL)、增塑剂甘油 (20,40,60 ,80 mg/mL)、海藻酸钠 (5,7.5,10,12.5 mg/mL) 以及CMC-Na (5,7.5,10,12.5 mg/mL)的用量,按“2.1.1”项下方法配制药液A,B。分别将药液A、B均匀喷涂于培养皿表面,37 ℃下记录成膜时间,对药液处方进行优化。

    参照《中华人民共和国药典》(2020年版)四部制剂通则方法及文献方法[1516],测定药液A、药液B的pH。对药液A、药液B分别进行连续喷射,观察喷雾效果,记录喷雾状态。分别取适量药液A、药液B置于离心管中,以4000 r/min 的转速离心15 min,观察药液A、药液B离心前后的溶液状态,评价其离心稳定性。分别取适量药液A、药液B,室温放置1周,测定其含量及喷雾状态,对其储存稳定性进行评价。

    按“2.1”项下优化的处方分别配制药液A和药液B,使用时先按压喷涂一定量的药液B,再喷涂一定量药液A至同一位置,于37 ℃保持一定时间,即可成膜。

    以成膜时间和黏附性能为指标,对药液A和药液B比例进行优化。具体操作如下,分别考察不同药液B与药液A比例处方(1∶2,1∶1和2∶1)形成原位膜的成膜时间。将铺有药膜的平板竖直放置,每隔20 分钟 向药膜平板喷洒0.2 mL 水保湿,记录药膜从平板表面脱落时间,评价药膜的黏附性能。

    采用最优处方制备复方碘口腔喷雾原位膜,记录体内外成膜时间,观察其外观及拉伸性能。冷冻干燥,扫描电镜下观察其微观结构。

    复方碘口腔喷雾原位膜,干燥至恒重后取1 g 药膜于无水乙醇中溶解,超声后振荡4 h,过滤除去不溶性杂质,测定滤液的吸光度,计算复方碘喷雾原位膜中碘含量。

    按“2.2”项下方法制备复方碘口腔喷雾原位膜。干燥离心管称重,记录为m0,将制备好的膜剂置于干燥的离心管中,干燥至恒重,称量总重为m1。在离心管中加入人工模拟唾液(Na2HPO4 2.38 g,KH2PO4 0.19 g,NaCl2 10.8 g溶于1000 mL蒸馏水中),室温下放置24 h 后过滤,将未溶解的残渣置于离心管中干燥至恒重,称量总重m2。膜的溶解性=[(m1m2)/(m1m0)]×100%。

    按“2.3”项下方法制备复方碘口腔喷雾原位膜。空白离心管干燥至恒重,记录为m0,将制备好的药膜置于离心管中,干燥至恒重,称量总重m1。再将干燥至恒重的药膜及离心管与饱和氯化钠溶液共同置于密封的容器内,室温下放置24 h后,称量膜和离心管的总重m2。膜的吸湿性=[(m2m1)/(m1m0)]×100%。

    参照文献[17]方法,测定复方碘喷雾原位膜的吸湿性能。按“2.3”项下方法制备复方碘口腔喷雾原位膜。将制备好的膜干燥至恒重,称量膜重M0。将干燥膜放入盛有饱和碳酸钾溶液的密闭容器中,室温下放置24 h 后,用滤纸吸去表面水分,称重m1。再将润湿后的膜放入装有无水氯化钙的密闭容器中,室温下继续放置24 h,称重记录为m2。膜的保湿性=[(m2m0)/(m1m0)]×100%。

    将碘甘油(含碘200 mg)包封于软胶囊制备碘甘油软胶囊剂,将复方碘喷雾原位膜(含碘200 mg)分别置于人工唾液50 mL中,37 ℃,170 r/min条件下持续振荡。在一定时间间隔内取出溶液1 mL,并加入等量的新鲜人工唾液。采用紫外分光光度法测定溶出液中的碘浓度,计算得到不同时间点释放的碘浓度。以时间为横坐标,碘累计释放率为纵坐标,绘制释放曲线。

    参照文献方法[18],采用 MTT实验考察成膜材料的生物相容性。3T6细胞采用高糖DMEM为培养基,培养条件为37 ℃、5% CO2浓度下恒温孵育。具体操作为:取对数生长期的细胞接种于96孔板,每孔5 × 104 个细胞,孵育24 h 后吸去培养基,将空白口腔喷雾原位膜用无血清DMEM培养基溶解稀释后加入相应孔中,分别孵育24和48 h后,吸去培养液,每孔加入MTT (5 mg/mL) 溶液100 μL,继续孵育4 h 后将MTT吸出,每孔加DMSO 200 μL,37 ℃ 振摇5 min,酶标仪测定490 nm 波长处的吸收度。未给药的细胞作为空白对照组,给予无血清培养基进行孵育。

    采用划痕实验考察空白膜和复方碘口腔喷雾原位膜对细胞迁移能力的影响。具体操作为:取对数生长期的3T6细胞接种于6孔板,每孔1×105 个细胞,孵育24 h。用200 μL移液枪枪头尖端垂直划伤细胞表面,用无血清DMEM培养基洗涤,采用倒置荧光显微镜拍摄细胞划痕情况。将空白和载药膜用无血清DMEM培养基溶解稀释后加入6孔板,分别孵育12 和24 h后,拍摄细胞迁移情况,计算细胞迁移率,评价成膜材料的促生长能力。

    参照文献方法[19],建立兔口腔溃疡模型。具体操作如下,兔麻醉后暴露兔唇处黏膜,用浸泡过50% 冰醋酸的湿棉花腐蚀黏膜60 s,即得兔口腔溃疡模型。兔子随机分为4组,分别为模型组(造模后在伤口处给予生理盐水)、空白药膜组、复方碘制剂组和含复方碘药膜组。各组每次给药后用手指将制剂按在溃疡区干预20 min,每隔1天处理伤口1次,连续处理7 d。一定时间间隔观察口腔溃疡的愈合情况。

    所有实验数据使用Graph Pad Prism 8.0软件进行统计分析,实验结果均表示为$\bar{x} $ ± s,采用One-Way ANOVA进行组间分析。P < 0.05代表组间差异具有统计学意义。

    以成膜时间为指标,对药液A及药液B处方进行优化。如图1-A~1-D所示,分别为Eudragit L-100、氯化钙、甘油、海藻酸钠和CMC-Na用量对成膜时间的影响。结果显示,当Eudragit L-100、氯化钙、甘油、海藻酸钠、CMC-Na用量分别为50,7.5,60,12.5和12.5 mg/mL 时,相对应处方的成膜时间均为最短。但考察时发现,当海藻酸钠和CMC-Na用量为12.5 mg/mL 时,溶液的喷射状态是线状并非喷雾状,影响成膜性能,因此CMC-Na用量选用10 mg/mL。根据单因素试验得出的最优处方为:A液中, Eudragit L-100 50 mg/mL,CaCl2 7.5 mg/mL,甘油60 mg/mL,B液中,海藻酸钠12.5 mg/mL,CMC-Na 10 mg/mL。

    Figure  1.  Film formation time of film sprays
    A: Eudragit L-100; B: Calcium chloride; C: Glycerin; D: Sodium alginate; E: CMC-Na

    按项“3.1”项下优化处方分别配制药液A及药液B,如图2-A、2-B。药液A为透明澄清的均一溶液,药液B为黄色澄清的均一溶液。药液A和药液B的pH平均值分别为6.21 ± 0.02和6.42 ± 0.03 。口腔黏膜的正常pH为6.2~7.6,可见喷膜剂药液的pH适宜。

    Figure  2.  Quality evaluation of compound iodine oral spray
    A: Character of liquid A; B: Character of liquid B; C: State of the solution before centrifugation; D: State of the solution after centrifugation

    药液A和药液B的连续喷射,喷雾状态结果显示药液A呈雾状喷出,药液B呈半雾状喷出,两者喷射状态均表现良好,不会在喷口处发生凝结。

    离心稳定性实验结果如图2-C、2-D所示,药液A及药液B离心后均未发生分层,且外观均匀一致,呈透明溶液状态,表明药液A及药液B均具有良好的动力学稳定性。

    分别对药液A、空白药液B和含碘药液B进行全波长扫描,确定碘在292 nm具有最大吸收,与文献报道一致[20],且辅料无干扰。因此选择292 nm 波长为碘的测定波长,采用紫外分光光度法建立标准曲线,线性回归方程为:Y = 90.438 X0.1173 (R² = 0.996),回收率为(98.62 ± 0.63)%,且回收率和精密度测试结果的RSD均小于2%,符合体外方法学的规定。药液B中碘的含量为(1.96 ± 0.01)mg/mL。

    药液A和药液B放置1周后喷射状态均保持良好,其中药液B的碘含量为(1.95 ± 0.02)mg/mL。

    以上结果表明复方碘口腔喷雾药液,适于口腔黏膜使用,且具有良好的稳定性。

    单因素实验优化结果如图3-A所示,药液B的比例逐渐升高时,成膜时间从102 s延长至143 s,当药液B与药液A比例为1∶2时,成膜最快,但此时药膜的黏附性最差,仅3.3 h 便发生脱落。可能是由于药液B涂层过薄,药液A与药液B接触混合较快且药液A过量造成药膜黏度不够所致。因此,综合成膜时间和药膜的黏附性,药液B和药液A的喷涂比例选择1∶1,此时,药液的成膜时间为110 s,且在湿润环境下保持近5 h 才发生脱落,具有较好的黏附性。

    Figure  3.  Preparation and prescription optimization of drug film
    A: Results of film formation time and adhesion properties (n=3); B: Plan view of drug film; C: Side view of drug film; D: SEM of the drug film

    采用最优处方制备的复方碘口腔喷雾原位膜如图3-B、3-C所示,药膜在体外的成膜时间为(118.3 ± 3.6) s,在体内的成膜时间为(133.3± 4.6) s;药膜呈厚度均一的平整黄色薄膜,具有良好的可拉伸性,适于口腔黏膜的应用需求。

    以1∶1比例喷涂药液A和药液B形成复方碘口腔喷雾原位膜,冻干后在扫描电镜下观察其形态,如图3-D所示,药膜表面具有多孔洞结构,符合凝胶特性。

    复方碘口腔喷雾原位膜中碘-碘化钾复合物的含量为(47.42 ± 0.39)mg/g,平均标示量在96.83%~99.61%,收率为(99.80 ± 0.47)%,且回收率和精密度结果RSD均小于2%,符合药典相关规定要求。

    复方碘口腔喷雾原位膜的溶解性、吸湿性和保湿性实验结果显示,原位膜在人工唾液中24 h的溶解率为(87.31 ± 1.74)%,无大颗粒残渣,表明原位膜溶解性能较好,有利于在使用过程中药物缓慢释放且不会存在较大异物感。原位膜的吸湿性为(124.17 ± 7.13)%,表明原位膜具有较好的吸湿性,有利于吸收伤口渗出液。同时吸湿是保湿的基础,能够加快药物渗透入伤口内,从而发挥更好的药物疗效。原位膜的保湿性约为(26.85 ± 2.50)%,有利于保持伤口的润湿,促进愈合。

    复方碘口腔喷雾原位膜在体外的释放情况如图4所示,在2 h 时,碘甘油软胶囊就已经几乎完全崩解释放出90%的制剂。而5 h 时,药膜中复方碘的释放仅为25%,18 h后释放趋于平稳,30 h 后药膜中复方碘在人工唾液中的累计释放率为90%。表明复方碘口腔喷雾原位膜具有缓释作用,有利于延长药物作用时间。

    Figure  4.  In vitro release results of iodine-glycerol soft capsules andpharmaceutical films($\bar{x} $ ± s, n=3)

    成膜材料对3T6细胞作用不同时间后的细胞存活率如图5-A所示。结果显示,在考察的浓度范围内,细胞的存活率均大于95%,表明成膜材料具有良好的生物相容性。而相同浓度下,处理48 h的细胞存活率均高于处理24 h 的细胞,且细胞存活率大于100%,表明空白膜材料具有一定的促生长能力。细胞划痕实验结果如图4-B、4-C所示,空白膜和含药膜处理组的细胞迁移率显著高于对照组(P<0.00 1),且含药膜显示出更高的细胞迁移率。细胞实验结果表明复方碘原位膜有助于成纤维细胞迁移,具有促进创面愈合的潜力。

    Figure  5.  Biocompatibility of free film($\bar{x} $ ± s, n=3)
    A: Cell viabilities of 3T6-Swiss albino treated with free film for 24 h and 48 h; B: Fibroblast migration behaviors; C: Fibroblast migration rates after treatment with free film**P < 0.01, ***P < 0.001

    各组实验动物口腔溃疡创面愈合情况如图6所示,与对照组相比,碘溶液组、空白膜组、复方碘药膜组在各时间点皆表现出促修复作用。且从第3 天开始,复方碘药膜组溃疡面积显著低于空白膜组及复方碘溶液组;在第5天 时,复方碘药膜组口腔溃疡创面已几乎愈合,创面修复面积显著低于复方碘溶液组(P<0.00 1)。结果表明:复方碘溶液在兔口腔黏膜显示出良好的原位成膜效果,空白膜材对溃疡创面具有一定的保护和促修复作用;复方碘药膜与复方碘溶液相比,具有更佳的促口腔溃疡促修复效果。

    Figure  6.  Therapeutic effect of drug film on oral ulcer of rabbit
    A: Image of oral ulcer healing process in animal model; B: Quantitative results of oral ulcer healing process($\bar{x} $ ± s, n=3)*P < 0.05, ***P < 0.001 vs drug film group

    用于制备凝胶膜剂的材料种类较多,在预实验中对成膜材料进行筛选,发现壳聚糖、卡波姆和明胶易呈凝胶状态,泊洛沙姆和乙基纤维素虽然呈溶液状态,但成膜性均较差,不能单独成膜,不适合作为喷膜剂材料。聚乙烯醇、羟丙基甲基纤维素、聚乙烯吡咯烷酮、聚丙烯酸树脂等材料的成膜性能较好,且溶解后均为溶液状态,能以喷雾的形式喷出,但聚乙烯醇、羧甲基纤维素钠及聚乙烯吡咯烷酮成膜时间过长。通过成膜性能、喷雾状态和成膜时间综合评价,选择以海藻酸、聚丙烯酸树脂和CMC-Na作为混合膜材成膜材料。

    口腔膜剂给药方便,顺应性好,近年来受到广泛关注,美国已有80多个品种获批。我国目前有阿立哌唑口溶膜、昂丹司琼口溶膜等4款口溶膜获批上市,口腔膜剂具有巨大的市场前景。口腔溃疡患者数量大,但目前用于口腔溃疡的新型制剂研究匮乏。本研究开发了复方碘口腔喷雾原位贴膜,在溃疡处快速形成原位贴膜,对溃疡部位起到保护作用,使用方便,具有缓释作用,可有效促进创面修复。此外,在材料安全性评价中发现,空白膜材对细胞生长具有促进作用;在兔口腔溃疡治疗中,空白膜组也显示出对溃疡黏膜的促修复作用。推测这是由于材料中的海藻酸的促增殖作用,与文献报道一致[2122]。因此本研究所制备的复方碘口腔喷雾原位贴膜可能通过抗菌及材料的促增殖的双重作用促进溃疡修复。相关机制将在后续实验中进行深入研究。

  • Figure  1.   Parent nucleus structures (A−E)

    Figure  2.   Total ion current diagram of each brand of Span

    A: Span 85; B:Span 80; C: Span 60; D: Span 40; E: Span 20

    Figure  3.   Comparison of total ion current of Span 80 from different manufacturers

    A: Pharmaceutical excipients manufacturer Span 80; B: Reagent manufacturer Span 80

    Figure  4.   Comparison of total ion current of Span 80 from different manufacturing techniques

    A: Manufacturing technique 1; B: Manufacturing technique 2

    Table  1   Determination results of fatty acid composition of each brand of Span

    Name of fatty acidsNormalization results/%
    Span 20Span 40Span 60Span 80Span 85
    Methyl caproate0.1////
    Methyl caprylate4.7////
    Methyl decanoate5.4////
    Methyl laurate52.5//0.12/
    Methyl myristate19.9//0.292.8
    Palmitic acid methylester99947.14.974.3
    Methylcis-9-hexadecenoate////4.8
    Methyl stearate5.3/481.541.1
    Methyl oleate///79.2870.8
    Methyl linolenate2//13.2312.9
    下载: 导出CSV

    Table  2   Span 20 structure speculation

    No. m/z Parent nucleus structure Inferred R basis
    1 477.29 A Octanoic acid root,laurate root or decanoate root,laurate root
    2 505.32 A Octanoic acid root,myristic acid root or decanoate root,laurate root
    3 533.35 A Decanoate root,myristic acid root or laurate root,laurate root   or octanoic acid root,palmitate root
    4 561.39 A Laurate root,myristic acid root or decanoate root,palmitate root or octanoic acid root,stearate root
    5 589.42 A Decanoate root,stearate root or laurate root,palmitate root or myristic acid root,myristic acid root
    6 351.19 B Laurate root and H
    7 379.22 B Myristic acid root and H
    8 733.53 C Octanoic acid root,decanoate,stearate root or octanoic acid root,laurate,palmitate or octanoic acid root,myristic acid root,myristic acid root or decanoate,decanoate,palmitate or decanoate,laurate,myristic acid root or laurate,laurate,laurate
    9 435.28 A Stearate root
    10 789.59 C Octanoic acid root,myristic acid root,stearate root or octanoic acid root,palmitate root,palmitate root or decanoate root,laurate root,stearate root or decanoate root,myristic acid root,palmitate root or laurate root,laurate root,palmitate root or laurate root,myristic acid root, myristic acid root
    11 495.3 D Octanoic acid root,laurate root or decanoate root,decanoate root
    12 523.33 D Octanoic acid root,myristic acid root or decanoate root,laurate root
    13 407.25 B Palmitate root and H
    14 551.36 D Decanoate root,myristic acid root or laurate root,laurate root or octanoic acid root,palmitate root
    15 579.39 D Octanoic acid root,stearate root or decanoate root,palmitate root or laurate root,myristic acid root
    16 607.42 D Decanoate root,stearate root or laurate root,palmitate root or myristic acid root ,myristic acid root
    17 635.45 D Laurate root,stearate root or myristic acid root,palmitate root
    18 313.14 E Octanoic acid root
    19 341.17 E Decanoate root
    20 369.2 E Laurate root
    21 397.23 E Myristic acid root
    下载: 导出CSV

    Table  3   Span 40 structure speculation

    No. m/z Parent nucleus structure Inferred R basis
    1 407.25 B Palmitate root and H
    2 393.27 E Myristic acid root
    3 901.71 C Myristic acid root,palmitate root,stearate root,laurate root,stearate root,stearate root or palmitate root,palmitate root,palmitate root
    4 791.53 C Octanoic acid root,palmitate root,linoleic acid root or decanoate root,myristic acid root,linoleic acid root or laurate root,laurate root,linoleic acid root
    5 663.48 D Myristic acid root,stearate root or palmitate root,palmitate root
    6 425.26 E Palmitate root
    7 631.50 A Laurate root,linoleic acid root
    下载: 导出CSV

    Table  4   Span 60 structure speculation

    No. m/z Parent nucleus structure Inferred R basis
    1 673.51 A Palmitate root, stearate root
    2 407.25 B Palmitate root and H
    791.53 C Octanoic acid root,palmitate root,linoleic acid root or decanoate root,myristic acid root,linoleic acid root or laurate root,laurate root,linoleic acid root
    3 701.54 A Stearate root,stearate root
    C Octanoic acid root,octanoic acid root,linoleic acid root
    4 435.28 B Stearate root and H
    847.59 C Decanoate root,stearate root,linoleic acid root or decanoate root,oleate root,oleate root or laurate root,palmitate root,linoleic acid root
    5 645.48 A Myristic acid root,stearate root or palmitate root,palmitate root or aurate root,stearate root,stearate root
    6 901.71 C Palmitate root,palmitate root,palmitate root or myristic acid root,palmitate root,stearate root
    7 929.74 C Myristic acid root,stearate root ,stearate root or palmitate root,palmitate root,stearate root
    8 663.49 D Palmitate root,palmitate root or myristic acid root,stearate root
    9 985.80 C Stearate root,stearate root,stearate root  
    10 957.78 C Palmitate root,stearate root ,stearate root  
    C Stearate root,oleate root,linoleic acid root  
    11 425.26 E Palmitate root
    12 691.52 D Palmitate root,stearate root
    13 719.55 D Stearate root,stearate root
    下载: 导出CSV

    Table  5   Span 80 structure speculation

    No. m/z Parent nucleus structure Inferred R basis
    1 671.49 A Oleate root,palmitate root
    A Linoleic acid root,linoleic acid root
    2 695.49 A Oleate root,linoleic acid root
    D Oleate root,stearate root or stearate root,linoleic acid root
    3 697.51 A Oleate root,oleate root
    D Stearate root,stearate root
    4 431.25 B Linoleic acid root and H
    5 433.27 B Oleate root and H
    6 977.74 C Stearate root,linoleic acid root ,linoleic acid root or oleate root,oleate root,linoleic acid root  
    7 979.76 C Stearate root,oleate root,linoleic acid root or oleate root ,oleate root,oleate root
    8 715.52 D Oleate root,oleate root stearate root,linoleic acid root
    9 713.5 D Oleate root,linoleic acid root
    下载: 导出CSV

    Table  6   Span 85 structure speculation

    No. m/z Parent nucleus structure Inferred R basis
    1 643.46 A Myristic acid root,oleate root or palmitate root ,palm oil acid root
    2 669.48 A Palmitatet,linoleic acid root or palm oil acid root ,oleate root
    3 695.49 A Oleate root,linoleic acid root
    D Oleate root, stearate root
    4 697.51 A Stearate root,linoleic acid root or oleate root ,oleate root
    D Stearate root
    5 433.27 B Oleate root and H
    6 715.52 D Stearate root,Linoleic acid root or oleate root,oleate root
    7 979.76 C Stearate root,oleate root,linoleic acid root or oleate root,oleate root,oleate root
    8 953.74 C Palmitate,stearate root ,linoleic acid root or palmitate root,oleate root,oleate root or palm oil acid root,oleate root,stearate root
    C Oleate root,linoleic acid root,linoleic acid root
    9 641.45 A Myristic acid root,linoleic acid root
    D Myristic acid root,stearate root or palmitate root,palmitate root
    下载: 导出CSV
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  • 收稿日期:  2024-01-04
  • 刊出日期:  2024-12-24

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