中成药、保健食品中非法添加诺氟沙星的快速检测方法研究

目的建立一种简单、快速、准确的检验方法鉴别、筛查出治疗前列腺疾病的中成药及保健食品中是否非法添加诺氟沙星药物。方法采用薄层色谱法（TLC）、高效液相色谱法（HPLC）等检测方法对治疗前列腺疾病的中成药及保健食品中非法添加诺氟沙星抗生素进行快速鉴别、分析研究。结果能准确筛查出治疗前列腺疾病的中成药及保健食品中非法添加的诺氟沙星抗生素成分。结论建立的检测方法简单、快速、准确,能应用于这一类假劣药品的日常监督、快速分析。     

保健食品中非法添加化学药品检测方法研究进展

摘要近年来,保健食品的发展速度很快,非法添加化学药品的现象也比较严重。整理分析国内外保健食品中非法添加化学药品的检测方法文献,为保健食品中非法添加化学药品的检验工作提供参考。目前分析方法发展比较缓慢,因此,建立有效、快速的检测方法具有重要的现实意义。     

保健食品中非法添加化学药物的检测方法

对市场上常见保健食品（声称减肥、缓解体力疲劳、辅助降血糖、改善睡眠四类）中非法添加化学药物进行筛查方法总结,为相关监管部门及时发现非法添加行为提供技术支持,保证消费者服用保健食品的安全.     

保健食品中非法添加药物的检测方法的研究

保健食品是指具有特定保健功能或者以补充维生素、矿物质为目的的食品,适宜于特定人群食用,具有调节肌体功能,不以治疗疾病为目的,并且对人体不产生任何急性、亚急性或者慢性危害的食品.保健食品属于食品范畴,有一定功效,长期食用安全无害;保健食品不是药品,不以治疗疾病为目的.调查显示,为了提高产品的功能效果,一些不法厂商向保健食品中非法添加各种化学合成药物的行为屡有发生,这些药物对人体有明显的副作用.加强对保健食品或中成药中非法添加的化学药品的分析检测,可以提高药品监督管理部门对流通环节中假劣药品或保健品的监管,使制售假药违法行为得到有效遏制.近年来,采用现代分析技术,建立了保健食品中非法添加减肥药、降糖药、降压药、镇静催眠药等多种化学药品的定性、定量检测等方法,现做一综述.     

常见中成药和保健食品中非法添加化学物质的检测方法研究进展

综述了常见的降糖、壮阳补肾和减肥这三类中成药和保健食品中非法添加化学物质的检测方法,以便为相关药品监管部门及时发现这种非法添加行为提供技术支持,保证患者用药的安全.     

UPLC-MS/MS检测乌鸡白凤丸中非法添加西洋参

目的建立UPLC-MS/MS测定乌鸡白凤丸中非法添加的西洋参。方法使用Waters ACQUITY BEH C18色谱柱(2.1 mm×100 mm,1.7μm),以乙腈和水为流动相,梯度洗脱,流速为0.35 mL·min^-1,柱温40℃,电喷雾电离源(ESI-),多反应离子监测(MRM)扫描方式进行检测。结果拟人参皂苷F11在0.113 0~451.9 ng·mL^-1范围内线性关系良好(r=0.999),重复性的相对标准偏差为3.5%,拟人参皂苷F11平均加样回收率(n=9)为96.9%,检出限为0.1ng·mL^-1,定量限为0.4 ng·mL^-1。结论所建立的方法快速准确、灵敏度高,可用于乌鸡白凤丸中非法添加西洋参的筛选和检测。     

磷酸可待因非法添加快速检测方法研究

目的:建立一种磷酸可待因非法添加的化学快检方法.方法:以拟定的快检方法作为初筛方法,高分离度快速液相四极杆串联飞行时间质谱法(RRLC-QTOF-MS)作为最终确证方法.结果:30批样品阳性检出率为100％,假阴性为0％,真阴性率为89.3％,假阳性率为10.7％,方法的检测灵敏度为0.12 mg.结论:该化学快检方法专属性强,灵敏度高,可提高抽样命中率,对磷酸可待因的非法添加起到监督作用.     

中成药、保健食品中非法添加化学成分的检测

通过对近年来的相关文献及传媒报道进行分类、分析，总结检测中成药、保健食品中非法添加化学成分的方法，为监管部门杜绝中成药、保健食品中非法添加化学成分的现象提供有效的技术支持。     

19F核磁共振定量法测定含氟漱口液中氟化钠的含量

目的 建立¹⁹F核磁共振技术测定含氟漱口液中氟化钠含量的方法。方法 采用¹⁹F核磁共振技术,以三氟乙酸作为内标物,使用300MHz核磁共振波谱仪,在25℃下采集样品的¹⁹F核磁共振谱,建立内标标准曲线,用于氟化钠定量分析。结果 氟化钠在0.1~0.8 mg/ml范围内,线性关系良好,回归方程为A=1.1392C-0.0013,r=0.99995;低、中、高3个浓度的平均回收率分别为99.36%、99.31%、99.65%,RSD分别为0.51%、0.35%、0.54%,含氟漱口液中氟化钠的平均含量为99.30%。结论 研究建立的¹⁹F核磁共振方法准确度、精密度较好,能够快速、准确地测定含氟漱口液中氟化钠的含量。     

LC-TOF/MS检测功能性红曲中非法添加异源洛伐他汀的研究

目的 建立基于LC-TOF/MS技术的分析方法,检测功能性红曲中非法添加非红曲来源的洛伐他汀。方法 红曲样品的甲醇提取物经Zorbax SB-C₁₈（4.6 mm×150 mm,5 μm）色谱柱,以0.05%甲酸水溶液-乙腈为流动相梯度洗脱（0~40min,40%~100%乙腈）,正离子扫描检测。结果 非法添加非红曲来源的洛伐他汀的功能性红曲存在天然功能性红曲没有的特征杂质离子峰,可以区分非法添加非红曲来源的洛伐他汀的功能性红曲和天然功能性红曲。结论 本方法可用于天然功能性红曲是否非法添加非红曲来源的洛伐他汀的鉴别。     

Generic ciprofloxacin tablets contain the stated amount of drug and different impurity profiles: A 19F, 1H and DOSY NMR analysis

The objective of this study was to control the purity of 16 commercial formulations of ciprofloxacin tablets purchased in different countries or via the Internet using 19F and 1H nuclear magnetic resonance (NMR). Twelve out of the sixteen commercial formulations of ciprofloxacin measured by 19F NMR contain the active ingredient within 100+/-5% of stated concentration. Three formulations have a lower ciprofloxacin content between 90 and 95% and one shows a higher concentration superior to 105%. The impurity profile was characterised using 19F and 1H NMR, and is characteristic of the manufacturer. Four to twelve fluorinated impurities among them fluoride ion and two already known compounds were detected and quantified in the sixteen formulations analysed by 19F NMR. Two other non-fluorinated impurities were observed in the seven formulations analysed with 1H NMR. The total content of impurities as well as their individual levels are in agreement with those reported previously in the few studies devoted to ciprofloxacin purity. However, all the formulations do not comply with the limits for impurities given in the ciprofloxacin monograph of the European Pharmacopeia. Finally, a "signature" of the formulations was obtained with Diffusion-Ordered SpectroscopY (DOSY) 1H NMR which allowed the characterisation of some excipients present in the formulations studied.     

Application of LC-NMR and HR-NMR to the characterization of biphenyl impurities in the synthetic route development for vestipitant,a novel NK1 antagonist

Vestipitant (1) is a novel NK1 antagonist currently under investigation for the treatment of CNS disorders and emesis. The first synthetic step comprised a Grignard synthesis. An impurity was identified and initially expected to be a symmetric biphenyl. This paper reports the work to synthesise the supposed structure and the spectroscopic analyses (LC-NMR and HR-NMR) to correctly identify the real structure and understand the chemical pathway of the impurity.     

DART-MS/MS法直接实时检测保健食品中非法添加的6个PDE5抑制剂的应用研究

目的:建立一种可以快速检测保健食品中非法添加6个磷酸二酯酶5(PDE5)抑制剂西地那非、他达拉非、红地那非、羟基豪莫西地那非、氨基他达拉非、伪伐地那非的方法。方法:采用直接实时分析(DART)离子源结合三重四极杆质谱,DART离子源的样品传输速度为0.2 mm·s-1,载气温度为450℃。Agilent 6410B Triple Quad LC/MS毛细管电压4 kV,干燥气流速为10 L·min-1。扫描模式为子离子全扫描,扫描范围为50～550 amu。待测成分的前体离子为m/z 475.1(西地那非),m/z467.2(红地那非),m/z 505.1(羟基豪莫西地那非),m/z 390.1(他达拉非),m/z 391.2(氨基他达拉非),m/z 460.3(伪伐地那非)。通过对照品与样品的二级质谱图对比进行样品中非法添加成分的定性鉴别。结果:若干批市售保健食品中有4批检出西地那非,1批检出他达拉非。检出限达1μg·g-1,检测时间仅为几分钟。结论:DART-MS可用于固体样品中添加PDE5抑制剂类成分的快速检测,用于药品快速检验中批量样品的初筛更有优势。     

研究药物对肿瘤细胞代谢的新方法──灌注细胞31P核磁共振谱

为连续观察药物对细胞代谢的影响,用含紫杉醇的灌注液对人口腔上皮癌KB细胞和人结肠癌HCT-8细胞在灌注条件下进行了细胞³¹P谱测定,从两种细胞在未给药、给药以及停药后的灌注条件下获得的代谢图谱中发现,紫杉醇使KB细胞和HCT-8细胞的ATP代谢水平均有升高,但KB细胞的ATP升高更为明显;同样剂量的长春新碱使KB细胞代谢中的ATP峰的改变不明显,推测可能与它们的作用机制不同有关。研究结果表明,灌注细胞³¹P谱测试法对观察药物对细胞代谢的作用是独特的。     

Biotransformation of lignan glycoside to its aglycone by Woodfordia fruticosa flowers: quantification of compounds using a validated HPTLC method

Context: Saraca asoca Linn. (Caesalpiniaceae) is an important traditional remedy for gynaecological disorders and it contains lyoniside, an aryl tetralin lignan glycoside. The aglycone of lyoniside, lyoniresinol possesses structural similarity to enterolignan precursors which are established phytoestrogens.

Objectives: This work illustrates biotransformation of lyoniside to lyoniresinol using Woodfordia fruticosa Kurz. (Lythraceae) flowers and simultaneous quantification of lyoniside and lyoniresinol using a validated HPTLC method.

Materials and methods: The aqueous extract prepared from S. asoca bark was fermented using W. fruticosa flowers. The substrate and fermented product both were simultaneously analyzed using solvent system:toluene:ethyl acetate:formic acid (4:3:0.4) at 254?nm. The method was validated for specificity, accuracy, precision, linearity, sensitivity and robustness as per ICH guidelines.

Results: The substrate showed the presence of lyoniside, however, it decreased as the fermentation proceeded. On 3rd day, lyoniresinol starts appearing in the medium. In 8 days duration most of the lyoniside converted to lyoniresinol. The developed method was specific for lyoniside and lyoniresinol. Lyoniside and lyoniresinol showed linearity in the range of 250–3000 and 500–2500?ng. The method was accurate as resulted in 99.84% and 99.83% recovery, respectively, for lyoniside and lyoniresinol.

Conclusion: Aryl tetralin lignan glycoside, lyoniside was successfully transformed into lyoniresinol using W. fruticosa flowers and their contents were simultaneously analyzed using developed validated HPTLC method.     

19F NMR as a powerful technique for the assay of anti-psychotic drug haloperidol in human serum and pharmaceutical formulations

19F nuclear magnetic resonance was used as a suitable analytical tool for the identification and selective determination of haloperidol in human serum and pharmaceutical preparations. The method is based on the integration of appropriate signals of haloperidol and trifluoroacetic acid as an internal standard. The proposed method is a rapid and facile, while without any sample pretreatment, manipulation of large samples and lengthy instrument time. The regression equation for haloperidol in human serum showed a good linearity in the range of 60-600 microg ml(-1) with a detection limit of 1.4 microg ml(-1). The mean recovery results on human serum samples ranged from about 96-103%, with relative standard deviations <8%. The method was also applied successfully to the determination of haloperidol in real pharmaceutical samples, and compared with the results obtained by a reference method. The drug's degradation was studied by the proposed method in hydrochloric acid media and main products were identified.     

Human urinary excretion of doxifluridine and metabolites during a 5-day chemotherapeutic schedule using fluorine-19 nuclear magnetic resonance spectrometry

The urinary excretion of doxifluridine (5 dFUrd) and its metabolites was determined during five days of chemotherapy using fluorine-19 nuclear magnetic resonance spectrometry. The daily urinary excretion of 5 dFUrd and its metabolites was high (-100% of the 5 dFUrd administered) and nearly constant through out the treatment. By far the major excreted compounds were unchanged 5 dFUrd and -fluoro--alanine which made up respectively -40% and -50% of the total. Neither accumulation of 5 dFUrd nor significant modifications in its metabolism were observed during the treatment.     

Quality assessment of fluoxetine and fluvoxamine pharmaceutical formulations purchased in different countries or via the Internet by 19F and 2D DOSY 1H NMR

A simple and selective (19)F NMR method has been validated for the quantitation of fluoxetine (FLX) and fluvoxamine (FLV) in methanol solutions and in human plasma and urine. The regression equations for FLX and FLV showed a good linearity in the range of 1.4-620 microg mL(-1) (3.3 x 10(-6)-1.8 x 10(-3) mol L(-1)) with a limit of detection of approximately 0.5 microg mL(-1) (1.3 x 10(-6) mol L(-1)) and a limit of quantification of approximately 2 microg mL(-1) (4.6 x 10(-6) mol L(-1)). The precision of the assay depends on the concentrations and is comprised between 1.5 and 9.5% for a range of concentrations between 1.2 x 10(-3) and 3.2 x 10(-6) mol L(-1). The accuracy evaluated through recovery studies ranged from approximately 96 to 103% in methanol solutions and in urine, and from approximately 93 to 104% in plasma, with standard deviations <7.5%. The low sensitivity of the method precludes its use for the assay of these antidepressants in biofluids at least at therapeutic doses as the ranges of FLX and FLV plasma levels are 0.15-0.5 microg mL(-1) and 0.15-0.25 microg mL(-1), respectively. The method was applied successfully to the determination of FLX and FLV contents in pharmaceutical samples (brand-named and generic) purchased in several countries or via the Internet. All the commercial formulations contain the active ingredient in the range 94-103% of stated concentration. A "signature" of the formulations (solid and liquid) was obtained with 2D Diffusion-Ordered SpectroscopY (DOSY) (1)H NMR which allowed the characterisation of the active ingredient and excipients present in the formulations studied. Finally, the DOSY separation of FLX and FLV whose molecular weights are very close was obtained by using beta-cyclodextrin as host-guest complexing agent.     

In vivo 19F nuclear magnetic resonance spectroscopy: a potential monitor of 5-fluorouracil pharmacokinetics and metabolism

Summary In vivo ¹⁹F nuclear magnetic resonance (NMR) spectroscopy has the potential to non-invasively measure the concentration of 5-fluorouracil (FUra) and some of its metabolites in humans. Such a measure could be useful in predicting and optimizing the response of individual patients treated with FUra. The ability of ¹⁹F NMR to monitor FUra metabolism in situ in rodent tumors and liver and in human liver has been demonstrated. However, the potential impact of this technique as a predictor of FUra response in individual patients is limited by both the sensitivity (i.e., limit of detection) and the resolution (i.e., ability to distinguish among magnetically similar metabolites) of NMR. To date, the ability of in vivo ¹⁹F NMR spectroscopy to provide information that can distinguish FUra-sensitive from FUra-insensitive tumors has not been established. This crucial point should be addressed in the immediate future in studies using the best of experimental conditions (i.e., optimum sensitivity and resolution in well-defined rodent tumor models with NMR methodology appropriate for measurement of absolute metabolite concentrations). The information gained from such studies and any new technical developments to enhance in vivo NMR sensitivity should be directly applicable to any future application of ¹⁹F NMR spectroscopy in clinical FUra therapy.