十二种国产麻黄的品质评价

本文应用高效液相色谱法对我国24个产地所产的12种麻黄生药进行了六种生物碱的定量分析,这六种生物碱是:麻黄碱(ephedrine),伪麻黄碱(pseudoephedrine),去甲基麻黄碱(norephedrine),去甲基伪麻黄碱(norpseudoephedrine),甲基麻黄碱(methylephedrine)和甲基伪麻黄碱(methylpseudoephedrine)。根据分析结果,对这些麻黄生药的品质作出了评价。     

HPLC-UV法同时测定麻黄中5种麻黄生物碱的含量

目的建立同时分离检测麻黄中麻黄碱(Ephedrine)、伪麻黄碱(Pseudoephedrine)、去甲麻黄碱(Norephedrine)、去甲伪麻黄碱(Norpseudoephedrine)和甲基麻黄碱(Methylephedrine)的含量测定方法。方法采用HPLC-UV法,色谱柱:苯基柱(Alltima Phenyl,250mm×4.6 mm,5μm);流动相:0.02 mol/L磷酸二氢钾溶液-乙腈(96∶4);流速:0.6 ml/min;检测波长:210 nm;柱温:25℃。结果 5种生物碱在13.5 min内即可达到完全分离,E在2.000 8～40.016 0μg/ml线性关系良好;PE在1.003 6～20.072 0μg/ml线性关系良好;NME在0.199 2～3.984 0μg/ml线性关系良好;NMP在0.200 0～4.00 0μg/ml线性关系良好;ME在0.200 4～4.008 0μg/ml线性关系良好。各生物碱的平均回收率均在92%～104%(RSD≤5.76%)。结论本方法可操作性强,简便快速,分离效果好,重现性好,可为麻黄及含麻黄的中西药制剂提供有效的检测手段。     

利用高效液相色谱法测定麻黄浸膏中几种麻黄碱的含量

目的:本文采用高效液相色谱法分离测定麻黄浸膏粉中去甲基麻黄碱,去甲基伪麻黄碱,麻黄碱,伪麻黄碱和甲基麻黄碱的含量.方法:最佳流动相组成磷酸二氢钠0.02mol/l(用盐酸和三乙胺调PH至3.2)-甲醇(99.8:0.2).检测波长210nm.流速1.5ml/min.柱温为室温.色谱柱为HIQSIL C18柱.结果:此法重现性较好,各组分均能达到基线分离,工作曲线线性良好.     

去甲伪麻黄碱的提取与转化

麻黄中含有十几种生物碱,其中有六种结构相似的生物碱:麻黄碱(一)Ephedrine、伪麻黄碱(+)Pseudo-ephedrine、甲基麻黄碱(-)N-Methylephedrine、甲基伪麻黄碱(+)N-Methylpseudo-ephedrine、去甲麻黄碱(-)Nor-ephedrine、去甲伪麻黄碱(+)Nor-pseudo-ephedrine为人们所熟知。目前国内麻黄碱、伪麻黄碱、甲基麻黄碱已由麻     

麻醉期间3种常用升压药物对SVV干扰规律的临床研究

目的 探索麻醉期间常用升压药物麻黄碱、去氧肾上腺素和去甲肾上腺素对心脏每搏输出量变异度(SVV)的具体干扰规律,为寻找合适的校正方法提供依据。方法 搜集60例择期行开颅手术的患者,随机纳入对照组(C组)、麻黄碱组(E组)、去氧肾上腺素组(D组)和去甲肾上腺素组(N组),绘制出各组的ΔSBP-ΔSVV曲线进行统计比较,并从数据库中选择回归方程来获得最佳曲线拟合公式。术毕比较各组的一般临床资料以及术后呕吐、新发昏迷、心律失常、肺炎、二次手术等术后不良事件发生率的差异。结果 3组升压药诱导的ΔSBP-ΔSVV变化曲线存在显著差异。E组最为特殊,表现为在血压上升阶段,ΔSVV先一过性升高后迅速压低;而在血压回落阶段,ΔSVV匀速回升。在各组内进行方程回归后显示,D组和N组的ΔSBP-ΔSVV曲线均最接近米氏方程,但同时N组采用单纯线性回归也可获得较高的拟合度。4组患者在术中一般资料、术后恢复情况及术后不良事件发生率方面,均没有统计学差异。结论 麻黄碱、去氧肾上腺素和去甲肾上腺素对SVV造成的干扰与其诱导的SBP升高之间,存在着各不相同的规律性。去甲肾上腺素相较于其余二者,其诱导的SBP升高与S...     

尿中麻黄碱类药物的HPLC定量分析

以甲基苯丙胺为内标,在C₁₈柱上,用高效液相色谱技术分离并同时测定了尿中6种麻黄碱类药物。在25min内,麻黄碱、伪麻黄碱、去甲麻黄碱、去甲伪麻黄碱、甲基麻黄碱、乙基麻黄碱和内标均达到基线分离,分离度大于1.80,且尿中其它杂质不干扰。方法回收率高,重现性好,在1.5～25μg/ml的浓度范围内有很好的线性关系,相关系数大于0.999。     

盐酸苯丙醇胺对鼻炎的疗效

苯丙醇胺(去甲麻黄碱)具有收缩外周血管作用。苯丙醇胺片口服后可缓解过敏性鼻炎患者的鼻塞;其1％溶液滴鼻,对鼻粘膜收缩的作用较同样浓度麻黄碱作用为强。经近期随访苯丙醇胺无快速耐受作用,也未发现有药物性鼻炎。     

华蟾蜍毒素增强5-羟色胺及拟交感胺对离体豚鼠输精管的收缩作用

华蟾蜍毒素(CB)10μmol·L~(-1)可促进5-羟色胺和酪胺使豚鼠输精管的收缩作用增强约3～4倍,经利血平及酚妥拉明处理后,则此增强作用明显减弱.CB也能明显增强麻黄碱及多巴胺对输精管的作用、唯正常输精管对此浓度几无反应,但输精管去神经以后,给此浓度时可立即出现节律性收缩.结果提示CB对豚鼠输精管的作用,可能存在微弱的直接作用和促进去甲肾上腺素释放的间接作用.     

高效液相色谱法测定体液中的N-去甲麻黄碱

N-去甲麻黄碱(Phenylpropanolamine,苯丙醇胺、简称PPA)是和麻黄碱相似的拟交感神经作用药物。与麻黄碱相比,其中枢兴奋作用和支气管扩张作用较弱而血管收缩作用较强。因此常配伍应用于治疗感冒,鼻     

麻黄碱对兔肺动脉条的作用机理

麻黄碱(Eph,0.1-3.0mM)。去甲肾上腺素(NE,0.05-50μM),酪胺(Tyr,0.03-0.3mM)均引起离体兔肺动脉条浓度依赖性收缩。6-羟基多巴胺(6-OH-DA)和可卡因(cocaine)预处理使Eph的作用分别减弱52.3±SD 12.6％和11.0±7.3％;Eph增加[~3H]NE从肺动脉壁的流出量,这一作用从给药后5min开始,持续20min以上。结果提示在兔肺动脉条上Eph兼有对效应器细胞的直接作用和通过解放NE的间接作用,其直接作用与间接作用大体相当。     

苯甲吗啉类药物的代谢及代谢产物的研究

本文报道苯甲吗啉类药物的气相色谱与气质联用检测方法。用HP-5890A气相色谱仪、氮专属性检测器,对服药后不同时间排尿中原型药及主要代谢产物,以内标法定量测定,绘制尿累积排泄曲线.醚提取物用三氟醋酐衍生化、气相色谱、气质联用分析比较衍生化前后保留时间及质谱数据,鉴定主要代谢产物苯甲吗啉,微量代谢产物去甲麻黄素、去甲伪麻黄素、麻黄素和伪麻黄素,方法灵敏、结果可靠,适用于此类药物的临床监测与运动员尿样检测。     

Simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, oxycodone, and 6-acetylmorphine in urine, serum, plasma, whole blood, and meconium by LC-MS-MS

A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for simultaneous analysis of six major opiates in urine, serum, plasma, whole blood, and meconium is described. The six opiates included are codeine, morphine, hydrocodone, hydromorphone, oxycodone, and 6-acetylmorphine (6-AM). The method was compared to an in-house gas chromatography (GC)-MS method and an LC-MS-MS method performed by another laboratory. The sample preparation time was decreased by eliminating the glucuronide hydrolysis and derivatization required for GC-MS analysis, as well as by adapting the solid-phase extraction to elute directly into autosampler vials. These improvements illustrate the advantages of an LC-MS-MS method over a GC-MS method for opiates. The structural similarity of these six opiates and others in the opiate class causes a high potential for interference and false-positive results. Twelve opiate analogues and metabolites were evaluated for interference. The potential for interference was reduced by altering the MRM transitions chosen for the six opiates. The increased specificity of LC-MS-MS decreased the interference rate in urine to 3.9% compared to 13.6% on the in-house GC-MS method. The rate of positivity for 6-AM in meconium is described for the first time. In urine, 11.0% of morphine positive specimens were also positive for 6-AM compared to 8.3% in serum/plasma and 0.9% in meconium. Although 6-AM is infrequent in meconium, it provides a definitive proof of illegal heroin abuse by the pregnant mother. This method has been routinely used in our laboratory over the last 6 months on more than 1500 patient specimens.     

Electrospray LC-MS method with solid-phase extraction for accurate determination of morphine-, codeine-, and ethylmorphine-glucuronides and 6-acetylmorphine in urine

A method for the identification and quantification of morphine-3-glucuronide, codeine-6-glucuronide, ethylmorphine-6-glucuronide, and 6-acetylmorphine in human urine based on solid-phase extraction (SPE) and electrospray ionization liquid chromatography-mass spectrometry (LC-MS) was validated for use as a confirmation procedure in combination with immunochemical screening for opiates. Three deuterium-labelled analogues were used as internal standards: morphine-3-glucuronide-d3, codeine-d3, and 6-acetylmorphine-d3. Fifty-microliter aliquots of urine were prepared by SPE using 30-mg Oasis HLB cartridges. The chromatographic system consisted of a 2.0 x 100-mm C18 column and the gradient elution buffers used acetonitrile and 25 mmol/L formic acid. The protonated molecular ions were monitored in the selected ion monitoring mode together with one qualifier ion for each analyte. The interassay variability was less than 10% at the reporting limit 30 ng/mL for 6-acetylmorphine and 300 ng/mL for the other analytes. The method was validated by comparison with a reference gas chromatographic (GC)-MS method using authentic urine samples. The two methods agreed completely regarding identified analytes, and for the quantitative results there were slightly lower levels when measuring glucuronides directly as compared to total determination after hydrolysis by GC-MS. This result was to be expected because the free compounds are not measured with the LC-MS method. This study concludes that the presented LC-MS method is robust and reliable, and suitable for use as a confirmation method in clinical urine drug testing for opiates.     

HPLC-ESI-ITMSn法鉴定麻黄碱及其大鼠体内主要代谢产物

目的建立快速灵敏的LC-ESI-ITMSⁿ分析检测麻黄碱及其大鼠体内代谢物的方法。方法以麻黄碱对照品对LC-ESI-ITMS²色谱及质谱条件进行了优化，分析总结其电喷雾质谱的一级电离规律和多级质谱裂解规律，以此作为麻黄碱大鼠体内代谢物分析鉴定的依据。健康大鼠空腹灌胃麻黄碱10 mg·kg^-1，收集0~48 h的尿样，经C₁₈小柱固相萃取分离纯化后，直接采用LC-ESI-ITMSⁿ方法对尿样进行测定。结果根据生物体内药物代谢转化规律及母体药物的色谱-质谱行为规律，在尿样中鉴定出3个第I相代谢产物，未发现第II相代谢产物。结论本方法灵敏、快速、选择性高、专属性好，可用于麻黄碱的代谢产物研究。     

The screening of forensic blood, urine, and tissue specimens for xenobiotics using ion-trap liquid chromatography-tandem mass spectrometry

During the investigation of aviation accidents, postmortem specimens from accident victims including blood, urine, and tissue are submitted to the Federal Aviation Administration's Civil Aerospace Medical Institute (CAMI) for toxicological analysis. The first, and perhaps most important, step in the analysis process is the initial screening of biological specimens for illicit, medically prescribed, and over-the-counter compounds that may be present and potentially be a cause and/or factor in the accident. Currently, our general unknown screening (GUS) procedure involves, in part, both gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC) with both diode-array detection (DAD) and fluorescence detection. Both GC and LC techniques have inherent limitations that prevent the detection of certain types of compounds. The decreased specificity and sensitivity of LC-DAD has been an impediment to the existing GUS procedure. Therefore, our laboratory set out to develop and validate an LC-MS-MS procedure that is superior to LC-DAD. The limits of detection of 359 forensically important xenobiotics have been established following solid-phase extraction from whole blood and analysis by LC-MS-MS. Although whole blood was used as the matrix during instrument validation, the method has been successfully applied to both forensic urine and tissue specimens as well.     

Urinary excretion of ephedrine after nasal application in healthy volunteers.

The urinary excretion of ephedrine after intranasal administration of the drug was studied in 8 healthy volunteers. Ephedrine (6 drops of a commercial 0.75% nasal ephedrine solution in each nasal cavity) was administered 4 times at intervals of 2 h (total amount applied equivalent to approximately 14 mg ephedrine), and urine was collected each hour for 10 h; the volunteers exercised on a bicycle ergometer at 50% of their VO2max for 2 h after the last ephedrine application. Ephedrine was detected in all urine samples. The urinary ephedrine concentration ranged from 0.9 to 16.5 micrograms mL-1; the number of urine samples with an ephedrine concentration exceeding 5 micrograms mL-1 ranged from 1/10 (volunteer 2) to 9/10 (volunteers 1 and 3). The mean percentage of dose recovered within 10 h was 33% (range 23-50%). There was a weak but significant negative correlation between urinary pH and amount of ephedrine in the urine; exercise did not consistently influence the urinary amount. These results illustrate the systemic availability of ephedrine upon intranasal administration and show that the therapeutic use of a nasal ephedrine formulation by an athlete on the day of a competition can lead to a urinary ephedrine concentration above 5 micrograms mL-1, which is considered positive in current doping regulations of the International Union of Cyclists.     

Screening for detection of new antidepressants, neuroleptics, hypnotics, and their metabolites in urine by GC-MS developed using rat liver microsomes

A gas chromatography-mass spectrometry (GC-MS) procedure for the detection of new antidepressants, neuroleptics, hypnotics, and their metabolites in urine is presented. The metabolites were first identified in rat liver microsome preparations by GC-MS after isolation and derivatization. Using these GC-MS data, a GC-MS screening was developed for urine as part of the authors' modified systematic toxicologic analysis procedure. After acid hydrolysis of a 2.5-mL aliquot of urine, a further aliquot was added. The mixture was then liquid-liquid extracted at pH 8-9, acetylated, and GC separated. Using mass chromatography with the ions m/z 58, 100, 120, 182, 195, 235, 261, 276, 284. and 293, the presence of new antidepressants, neuroleptics, hypnotics, and their metabolites could be indicated. Positive peaks could be identified by library search using the reference mass spectra recorded during the microsome studies. The intake of therapeutic doses of the following drugs could be monitored in urine: dosulepin, mirtazapine, moclobemide, nefazodone, trazodone, venlafaxine, and zolpidem. Olanzapine and zotepine were detectable in human urine only under steady-state conditions, and low-dose zopiclone was detectable only in overdose. The detection limit was less than 100 ng/mL (signal-to-noise ratio = 3) for the parent drugs.     

Detection of p-chloroamphetamine in urine samples with mass spectrometry

Designer drugs are introduced periodically to avoid detection and to provide new drugs with different pharmacological activities. During our routine analysis of amphetamine in urine samples, we observed one sample that reacted with immunoassay with high activity. There is one prominent peak in the gas chromatography- mass spectrometry (GC-MS) chromatogram. However, no amphetamine, methamphetamine, MDA, MDMA, MDEA, or ephedrine was detected with GC-MS. Careful examination of the mass spectrum indicated the presence of one fragment ion (m/z 140), which is similar to the base peak of trifluoroacetic anhydride derivative of amphetamine. The characteristic ion cluster representing the presence of one chlorine atom was observed. Investigation with liquid chromatography (LC)-MS detected an unknown compound with molecular ion of m/z 170. This compound was tentatively identified as chloroamphetamine. Pure standard material of p-chloroamphetamine (PCA) was purchased and analyzed with both GC-MS and LC-MS. Identical GC-MS spectra and LC-MS-MS fragmentation patterns were obtained. A GC-MS procedure was developed for the quantitation of PCA. The limits of detection and quantification were 10 μg/L. Precision was between 1.26% and 4.26%, and bias was between -0.91% and 4.27%. The prevalence PCA positive rate is 0.35% of the samples screened positive for amphetamine.     

Mechanistic pharmacokinetic modelling of ephedrine, norephedrine and caffeine in healthy subjects

AIM: The combination of ephedrine and caffeine has been used in herbal products for weight loss and athletic performance-enhancement, but the pharmacokinetic profiles of these compounds have not been well characterized. This study aimed to develop a mechanistic model describing ephedrine, norephedrine, and caffeine pharmacokinetics and their interactions in healthy subjects. METHODS: The pharmacokinetic model was developed based on the simultaneous modelling using plasma samples gathered from two clinical trials. The treatments consisted of single-doses of pharmaceutical caffeine and ephedrine, given alone or together, and an herbal formulation containing both caffeine and ephedrine. We used a mixed-effect statistical model and the program NONMEM to take account of intersubject variability. RESULTS: Three hundred and seventy-nine ephedrine, 352 norephedrine, 417 caffeine plasma concentrations and 40 ephedrine urine concentrations were obtained from 24 subjects. A one-compartment model with first-order absorption described the caffeine data. Caffeine clearance was 0.083 l min(-1) (CV 38%) and decreased to 0.038 l min(-1) in presence of oral contraceptive therapy, its volume of distribution was 38.6 l (CV 20%) and its absorption rate constant was 0.064 l min(-1) (CV 50%). A four-compartment model described the pharmocokinetics of ephedrine and norephedrine. Ephedrine was eliminated mostly renally, with a clearance of 0.34 l min(-1) (CV 11%), and a volume of distribution of 181 l (CV 19%). Nonlinearity in the conversion of ephedrine to norephedrine was observed. Different models showed that the simultaneous administration of caffeine, or the amount of caffeine in the absorption compartment, was associated with a slower rate of absorption of ephedrine. A 32% greater relative bioavailability of herbal compared with pharmaceutical ephedrine administration was observed. CONCLUSIONS: We describe a mechanistic model for ephedrine, norephedrine and caffeine pharmacokinetics and their interactions. The relative bioavailability of ephedrine differed between the herbal supplement compared with the pharmaceutical formulation. Concomitant ingestion of caffeine slowed the absorption rate of ephedrine, which is mainly related to the amount of the former in the absorption compartment. A saturable process appears to be involved in the metabolism of ephedrine to norephedrine.     

Rapid detection of benzoylecgonine in vitreous humor by enzyme immunoassay

The usual specimens submitted by a medical examiner for toxicological analysis include blood, urine, bile, vitreous humor, stomach contents, and solid-organ tissue. The detection of drugs in these specimens typically involves a combination of techniques including colorimetry, immunoassay, and gas chromatography. Although many laboratories rely principally on urine for the detection of drugs of abuse by immunoassay, these assays may be applied to other specimen types. An evaluation of Microgenics Corporation's cloned enzyme donor immunoassay (CEDIA) was conducted in order to evaluate its use in the detection of cocaine/cocaine metabolites in vitreous humor specimens. During a 14-month period, 392 vitreous humor specimens were analyzed by the CEDIA DAU Cocaine assay. Instrument parameters were set according to published manufacturer's guidelines. All presumptive positive immunoassay results prompted confirmatory testing and quantitation by gas chromatography-mass spectrometry (GC-MS) of other specimens including blood. Vitreous humor specimens were not tested by GC-MS. Using a approximately 100-ng/mL cutoff, the CEDIA assay produced 23 presumptive positive results, 22 of which were confirmed by GC-MS. The only specimen which could not be confirmed, elicited an immunoassay screen value near the cutoff limit. Routine analysis of blood, urine, bile, and/or bladder wash specimens by gas chromatography-nitrogen phosphorus detection revealed the presence of cocaine/cocaine metabolites in only 7 (31.8%) of the 22 confirmed cases. The concentration ranges of cocaine and benzoylecgonine in the blood specimens were none detected to 337 ng/mL and 17 to 8598 ng/mL, respectively. Cocaethylene was not detected in these cases. Analysis of vitreous humor specimens by CEDIA improved the detection rate of cocaine/cocaine metabolites by 0.7% in the cases submitted to our laboratory during the 14-month period.