复方盐酸伪麻黄碱缓释胶囊的薄层色谱鉴别方法

目的建立复方盐酸伪麻黄碱缓释胶囊薄层色谱鉴别方法。方法采用TLC法对复方盐酸伪麻黄碱缓释胶囊进行鉴别试验。结果TLC法分离出了该复方制剂中的盐酸伪麻黄碱和马来酸氯苯那敏。结论新建立的方法简便、灵敏、可行,分离效果好。     

Cetirizine/pseudoephedrine.

Cetirizine is the carboxylated metabolite of hydroxyzine, and has high specific affinity for histamine H(1) receptors. Pseudoephedrine is a sympathomimetic drug that acts directly on alpha-adrenergic receptors. black triangle Cetirizine/pseudoephedrine 5/120 mg twice daily was significantly more effective than intranasal budesonide 100 microg or placebo at improving nasal obstruction, nasal patency and reducing the volume of nasal secretion, and was significantly more effective than intranasal xylometazoline 0.1% with respect to nasal secretion, during house dust mite faeces challenge in three randomised, cross- over studies among volunteers with seasonal or perennial rhinitis. The onset of action of cetirizine/pseudoephedrine was reported to be approximately 30 minutes. black triangle The bioavailability of cetirizine and pseudoephedrine is similar after administration of cetirizine/pseudoephedrine 5/120 mg bilayer tablets or coadministration of cetirizine 5 mg tablets plus pseudoephedrine sustained-release (SR) 120 mg caplets. black triangle Cetirizine 5mg plus pseudoephedrine SR 120 mg twice daily for 2 to 3 weeks was significantly more effective than each drug given alone at reducing mean total symptom scores for seasonal or perennial allergic rhinitis in two randomised, double-blind, multicentre trials. In both studies, the mean proportion of days during which the five measured symptoms (nasal obstruction, sneezing, rhinorrhoea, nasal pruritus and ocular pruritus) were absent or mild was significantly greater in recipients of the cetirizine plus pseudoephedrine SR. black triangle In one study, cetirizine 5 mg plus pseudoephedrine SR 120 mg was significantly more effective at reducing nasal obstruction than either drug alone. black triangle Cetirizine 5mg plus pseudoephedrine SR 120 mg twice daily for 2 to 3 weeks was well tolerated in patients with seasonal or perennial allergic rhinitis. The most common adverse events were dry mouth, insomnia, headache, somnolence, asthenia and nervousness.     

Sensitive bioassay for the simultaneous determination of pseudoephedrine and cetirizine in human plasma by liquid-chromatography-ion trap spectrometry

A liquid chromatography-ion trap mass spectrometry coupled with electrospray ionization (HPLC-ESI-ion trap mass spectrometry) method for simultaneous determination of cetirizine and pseudoephedrine in human plasma is presented. Chromatographic separation was performed on a Hypurity C18 column (Thermo Hypersil-Keystone 2.1 mm x 150 mm, 5 microm, USA), The mobile phase was composed of 65% methanol and 35% water (contained 0.1% formic acid, 10 mM ammonium formate), which was run with a flow-rate of 0.2 ml/min at 40 degrees C. Quantitation was achieved by monitoring the product ions at m/z 166-->m/z 148 (pseudoephedrine), m/z 389.9-->m/z 201.1 (cetirizine), m/z 264-->m/z 246 (tramadol, IS). The calibration curve of pseudoephedrine and cetirizine was established with standard solutions. The limit of detection for pseudoephedrine and cetirizine each was 5 ng/ml. This simplified analytical method is sensitive, specific and accurate enough for simultaneous determination of pseudoephedrine and cetirizine in human plasma and is successfully applied to the pharmacokinetic study of pseudoephedrine and cetirizine.     

Effect of organic cations on the renal tubular secretion of pseudoephedrine in the rat

1. Pseudoephedrine is a weak organic base that undergoes renal tubular secretion. The aim of the present study was to assess whether two other commonly used weak organic bases (cimetidine and morphine) inhibit the renal tubular secretion of pseudoephedrine in the rat isolated perfused kidney. 2. A total of 12 perfusions were performed with four perfusions in each of three treatment groups. In the control group, pseudoephedrine was administered as a bolus dose of [14C]-pseudoephedrine and unlabelled pseudoephedrine to achieve an initial perfusate concentration of 0.4 microg/mL. For the treatment groups, pseudoephedrine was administered as above and cimetidine or morphine was added to the perfusion medium in increasing concentrations of 0.5-12.5 and 0.2-5.0 microg/mL, respectively. 3. The mean (+/-SD) fraction unbound of pseudoephedrine alone in perfusate was 0.866+/-0.014 and was not different (P> 0.05) in the presence of cimetidine or morphine. 4. In control experiments, the renal excretory clearance (CLR) of pseudoephedrine was three-fold greater than glomerular filtration rate (GFR), yielding a ratio consistently greater than unity, which indicates extensive net tubular secretion of pseudoephedrine. The CLR and total clearance of pseudoephedrine were similar, suggesting an absence of renal metabolism of pseudoephedrine. 5. The CLR/GFR ratio for pseudoephedrine was not affected by morphine, but was significantly reduced (P < 0.05) in the presence of cimetidine. 6. The results indicate that cimetidine inhibits the renal tubular secretion of pseudoephedrine.     

The influence of diuretics on the excretion and metabolism of doping agents: Part VI. Pseudoephedrine

A capillary gas chromatographic method with nitrogen specific detection is presented for measuring pseudoephedrine and its major metabolite norpseudoephedrine in urine after derivatization with trifluoroacetic anhydride. After the oral intake of 49.2 mg pseudoephedrine (ACTIFED) the active substance is nearly quantitatively excreted in urine over a 48 hr period. From 1 to 7 percent is metabolized to norpseudoephedrine. The intake of acetazolamide results in a suppression of the pseudoephedrine concentration for at least 12 h. The diuretic effect after the intake of 1.51 mineral water could be compared with the effect obtained with 1 mg bumetanide and results in a decrease in pseudoephedrine concentration by a factor 4 for several hours.     

复方盐酸伪麻黄碱溶液止咳作用及析方研究

目的 研究复方盐酸伪麻黄碱(盐酸伪麻黄碱 氢溴酸右美沙芬 扑尔敏)的止咳作用及组方的药理学基础。方法 通过小鼠氨水引咳实验及析方进行研究。结果 单用氢溴酸右姜沙芬具有止咳作用，而单用盐酸伪麻黄碱和扑尔敏无明显止咳作用；氢溴酸右姜沙芬与盐酸伪麻黄碱或扑尔敏合用均有协同止咳作用；复方盐酸伪麻黄碱三药间的协同作用大于它们的单用，并大于二药间的协同作用。结论 复方盐酸伪麻黄碱具有止咳作用，其蛆份可表现出明显的协同作用。     

星点设计-效应面法优化复方氯雷伪麻缓释片的缓释片芯处方

目的:优化复方氯雷伪麻缓释片的缓释片芯处方。方法:以氯雷他定加入包衣层并包衣硫酸伪麻黄碱片芯制备复方氯雷伪麻缓释片。采用星点设计-效应面法优化硫酸伪麻黄碱片芯处方,以单硬脂酸甘油酯(GM)和羟丙甲纤维素(HPMC)K15M用量为考察因素,以硫酸伪麻黄碱1、6、12 h的累积释放度为指标,通过重叠等高线图确定优化处方,并进行处方验证。结果:氯雷他定与欧巴代包衣粉按1∶3比例混合包衣成为速释层;硫酸伪麻黄碱片芯作为缓释层,其处方为每100片(600 mg/片)含硫酸伪麻黄碱12 g、GM 16.72 g、HPMC K15M 20.95 g、微晶纤维素9.73 g、硬脂酸镁0.6 g。优化处方所制制剂中氯雷他定15 min的累积溶出度为87.2%,硫酸伪麻黄碱1、6、12 h的累积释放度分别为34.20%、74.32%、94.60%。结论:缓释片芯处方合理、可行,所制备的复方氯雷伪麻缓释片具有缓释作用。     

Interpretation of urinary concentrations of pseudoephedrine and its metabolite cathine in relation to doping control

Until the end of 2003 a urinary concentration of pseudoephedrine exceeding 25 µg/mL was regarded as a doping violation by the World Anti‐Doping Agency. Since its removal from the prohibited list in 2004 the number of urine samples in which pseudoephedrine was detected in our laboratory increased substantially. Analysis of 116 in‐competition samples containing pseudoephedrine in 2007 and 2008, revealed that 66% of these samples had a concentration of pseudoephedrine above 25 µg/mL. This corresponded to 1.4% of all tested in competition samples in that period. In the period 2001–2003 only 0.18% of all analysed in competition samples contained more than 25 µg/mL. Statistical comparison of the two periods showed that after the removal of pseudoephedrine from the list its use increased significantly. Of the individual sports compared between the two periods, only cycling is shown to yield a significant increase. Analysis of excretion urine samples after administration of a therapeutic daily dose (240 mg pseudoephedrine) in one administration showed that the threshold of 25 µg/mL can be exceeded. The same samples were also analysed for cathine, which has currently a threshold of 5 µg/mL on the prohibited list. The maximum urinary concentration of cathine also exceeded the threshold for some volunteers. Comparison of the measured cathine and pseudoephedrine concentrations only indicated a poor correlation between them. Hence, cathine is not a good indicator to control pseudopehedrine intake. To control the (ab)use of ephedrines in sports it is recommended that WADA reintroduce a threshold for pseudoephedrine. Copyright © 2009 John Wiley & Sons, Ltd.     

高效液相色谱法测定人血浆中盐酸伪麻黄碱质量浓度

目的建立高效液相色谱法,用于测定人血浆中盐酸伪麻黄碱的质量浓度。方法采用内标法,以ODS柱（250 mm×4.6 mm,5μm）为固定相、60 mmol/L十二烷基硫酸钠、60 mol/L磷酸二氢钠水溶液（磷酸调pH=3.5）-乙腈（40∶60）为流动相,流速为1 mL/min,检测波长为213 nm。结果血浆中伪麻黄碱质量浓度在70～4 000μg/L范围内与峰面积比值线性关系良好（r=0.999 7）,最低检测浓度为0.012 5 mg/mL,方法提取率为69.01%。结论该方法具有较高的准确度,线性范围宽,方法灵敏,专一性好,操作简便,适用于盐酸伪麻黄碱血药浓度的测定及临床药代动力学研究。     

Pseudoephedrine: effects on milk production in women and estimation of infant exposure via breastmilk

AIMS: To assess the effects of pseudoephedrine on breast blood flow, temperature and milk production, and to estimate the likely infant dose during breastfeeding. METHODS: Eight lactating women (mean age 35 years and weight 69 kg) participated in a single-blind randomized crossover study of 60 mg pseudoephedrine hydrochloride vs placebo. Breast blood flow and surface temperature were measured from 0 to 4 h following the dose, and change in plasma prolactin was measured as the difference between predose and 1 h postdose concentrations. Milk production was measured for 24 h following placebo and pseudoephedrine. Infant dose of pseudoephedrine for a 60-mg dose administered four times daily to the mother was quantified as the product of average steady-state drug concentration in milk and an estimated milk production rate of 0.15 l x kg(-1) x day(-1) and expressed relative to the maternal weight-adjusted dose. RESULTS: There were no physiologically significant changes in breast blood flow or temperature between the placebo and pseudoephedrine periods. The mean change in plasma prolactin was slightly (13.5%), but not significantly lower (t = 1.245, P = 0.253) after pseudoephedrine (1775 mU x l(-1)) compared with placebo (2014 mU x l(-1)). However, the mean milk volume was reduced by 24% from 784 ml x day(-1) in the placebo period to 623 ml x day(-1) in the pseudoephedrine period (difference between means 161 ml x day(-1) (95% CI: 63, 259 ml x day(-1)); t = 3.9, P = 0.006). Assuming maternal intake of 60 mg pseudoephedrine hydrochloride four times daily, the estimated infant dose of pseudoephedrine was 4.3% (95% CI, 3.2, 5.4%) of the weight-adjusted maternal dose. CONCLUSIONS: A single dose of pseudoephedrine significantly reduced milk production. This effect was not attributable to changes in blood flow, but depression of prolactin secretion may be a contributing factor. At the maximum recommended pseudoephedrine doses, the calculated infant dose delivered via milk was < 10% of the maternal dose, and is unlikely to affect the infant adversely. The ability of pseudoephedrine to suppress lactation suggests a novel use for the drug.     

Effect of food on bioavailability of pseudoephedrine and brompheniramine administered from a gastrointestinal therapeutic system

The purpose of this study was to determine how a high-fat meal affects the delivery and absorption of pseudoephedrine and brompheniramine maleate when delivered from a gastrointestinal therapeutic system (GITS). This study was a randomized, complete crossover trial with 12 healthy male volunteers who were given single doses of the 24-h GITS under fed and fasted conditions. Pharmacokinetic parameters for both drugs were comparable between fed and fasted treatments, except for a shorter time to maximum concentration of pseudoephedrine for fed subjects (p = 0.002). Bioavailability of pseudoephedrine was 91% for fed relative to fasted treatment; for brompheniramine it was 89%. These results indicate that codelivery of the two drugs from the GITS is reliable and prolonged, and that the resulting absorption of pseudoephedrine and brompheniramine is minimally affected by food.     

Pseudoephedrine pharmacokinetics in the rat using a microanalysis technique.

A microanalytical procedure was developed using a gas chromatographic-electron capture technique which is capable of detecting 2 ng pseudoephedrine in 20 microliter plasma samples. Standard curves for pseudoephedrine are linear over the concentration range 0.1--1.6 microgram/ml. Plasma and urine concentrations of pseudoephedrine were followed in 3 rats after intravenous dosing. Derived pharmacokinetics parameters exhibited little inter-animal variation. Average plasma clearance was 67.6 ml/min/kg, with renal clearance averaging 30.3 ml/min/kg. This latter value is approximately 4X the glomerular filtration rate in the rat.     

Evaluation of the potential for pharmacodynamic and pharmacokinetic drug interactions between selegiline transdermal system and two sympathomimetic agents (pseudoephedrine and phenylpropanolamine) in healthy volunteers

Selegiline transdermal system is a recently approved monoamine oxidase inhibitor antidepressant. Medications that inhibit monoamine oxidase type A can augment the pressor effects of sympathomimetic amines, increasing the potential for hypertensive crisis. This study examined the potential for drug-drug interactions during treatment with selegiline transdermal system and pseudoephedrine or phenylpropanolamine. Two studies were conducted with 25 healthy volunteers to assess changes in blood pressure and heart rate during administration of pseudoephedrine or phenylpropanolamine alone or together with selegiline transdermal system. No significant differences in mean maximum changes in vital signs occurred with pseudoephedrine. No significant differences were found in mean maximum changes in systolic heart rate with phenylpropanolamine; however, 4 of 12 subjects each experienced 1 isolated protocol-defined minimal pressor response without concurrent adverse effects (1 with phenylpropanolamine alone; 3 with phenylpropanolamine + selegiline transdermal system). Pharmacokinetic parameters obtained following selegiline transdermal system and pseudoephedrine or phenylpropanolamine were unremarkable. The results suggest that selegiline transdermal system 6 mg/24 h does not significantly alter the pharmacodynamics or pharmacokinetics of either pseudoephedrine or phenylpropanolamine when administered to healthy volunteers; however, it is prudent to avoid coadministration of selegiline transdermal system and sympathomimetics.     

毛细管区带电泳法测定麻黄中麻黄碱和伪麻黄碱的含量

目的建立测定麻黄中麻黄碱和伪麻黄碱含量的毛细管区带电泳（CZE）法。方法以200 mmol.L-1硼砂-500 mmol.L-1硼酸溶液（1∶1,v/v）含2 mg.mL-1庚烷磺酸钠和0.4%（v/v）乙腈为背景电解质（BGE）,石英毛细管（75 cm×75μm）,有效分离长度60 cm,运行电压15 kV,紫外检测波长210 nm,重力进样20 s（高度10 cm）,以苯甲醇作内标,对麻黄中的麻黄碱和伪麻黄碱进行定量分析,以两者含量为参量对10批麻黄进行系统聚类分析并进行质量评价。结果麻黄碱和伪麻黄碱的相对峰面积（Ai/Ar）与各自的质量浓度C（mg.mL-1）呈良好的线性关系,两者的平均回收率分别为100.4%和100.9%。结论该法准确可靠,操作便捷,可用于麻黄中麻黄碱和伪麻黄碱的含量测定。     

HPLC法测定盐酸伪麻黄碱血药浓度

目的：建立盐酸伪麻黄碱血药浓度高效液相色谱法测定方法。方法：采用液-液萃取法,以对硝基苯胺为内标,测定盐酸伪麻黄碱血药浓度。在5例志愿受试者服药后测定了盐酸伪麻黄碱血药浓度,药代动力学参数用3P97程序计算。结果：盐酸伪麻黄碱在20～4000ng/ml范围内线性良好,得回归方程：Y=1180.1630X＋5.5970,r=0.9984,最低检出限20ng/ml,绝对回收率（91.61±8.07）%;内标总回收率（90.92±5.14）%,平均日内日间差5.98%。结论：测定方法灵敏、结果准确,可为临床血药浓度检测和药代动力学研究使用。     

A comparison of the bronchodilator action of pseudoephedrine and ephedrine in patients with reversible airway obstruction

Summary A double-blind randomised cross-over study was performed on 12 subjects suffering from reversible airway obstruction (asthma) to determine the relative bronchodilator effects of oral pseudoephedrine 60 mg, pseudoephedrine 180 mg, ephedrine 25 mg and matched placebo. Spirometry was used to measure vital capacity and forced expired volume in 1 s, and whole body plethysmography was used to measure specific airway conductance. Measurements were recorded before each drug was given, and 1 h and 2 h after each drug. Reversibility of the airway obstruction on each day of the study was demonstrated by significant improvements in all parameters of lung function in response to 400 µg of isoprenaline inhaled after the 2-h measurement. No significant bronchodilator effect could be shown following the ingestion of pseudoephedrine 60 mg or 180 mg. Only a week bronchodilator effect was demonstrated after ephedrine 25 mg in that the percentage change in vital capacity at 2 h after ephedrine was greater than that following either dose of pseudoephedrine or the placebo. It is concluded that oral pseudoephedrine in single doses of 60 mg or 180 mg has no significant bronchodilator action in man, and that a single dose of up to 180 mg pseudoephedrine does not cause tachycardia or hypertension.     

Pseudoephedrine, a sympathomimetic agent, induces Fos-like immunoreactivity in rat nucleus accumbens and striatum.

The pharmacological properties of the ephedrine derivative pseudoephedrine were investigated at the nuclear level. Following intraperitoneal injection of Sprague Dawley rats with pseudoephedrine, Fos induction was measured in various brain areas by Western blots and immunocytochemistry. Pseudoephedrine induced Fos-like immunoreactivity in the nucleus accumbens and striatum in a time and concentration-dependent manner with maximal effect at 60 mg/kg 2 h after injection. Immunocytochemical studies confirmed that the majority of the signal was detectable in the nucleus accumbens and striatum. Pre-injection with the D1 dopamine receptor antagonist SCH23390 partially and completely blocked pseudoephedrine-induced Fos-like immunoreactivity in the striatum and nucleus accumbens, respectively, suggesting that the action of pseudoephedrine is mediated via dopamine release and results in the activation of D1 dopamine receptors. With the exception of the higher doses required, the actions of pseudoephedrine were similar to those previously described for the psychostimulant amphetamine.     

Comparison of the effects of D-(-)-ephedrine and L-(+)-pseudoephedrine on the cardiovascular and respiratory systems in man.

1 In a preliminary double-blind trial the effects of ephedrine and pseudoephedrine on the blood pressure and heart rate of resting healthy volunteers were compared. Ephedrine 60 or 90 mg were required to raise the diastolic blood pressure above 90 mmHg, whereas 210 or 240 mg pseudoephedrine were required to produce the same effect. 2 In a second double-blind trial, patients with reversible airways obstruction were given 60 mg ephedrine or 210 mg pseudoephedrine and the effects on forced expiratory volume in one second (FEV1) compared. Both isomers produced some bronchodilation, but the effect of pseudoephedrine was less than half that of ephedrine. 3 The reasons for these differences between the isomers are discussed and the efficacy of pseudoephedrine as a nasal decongestant pointed out and explained in relation to its effect on alpha-adrenoceptors in the nasal blood vessels.     

肺宁合剂提取工艺中甘草和麻黄的配伍规律研究

目的研究肺宁合剂处方中甘草和麻黄的配伍规律。方法以各配伍样品中麻黄碱、伪麻黄碱含量为指标，采用高效液相色谱（HPLC）法测定。结果方中甘草在提取过程中减少了麻黄碱、伪麻黄碱的含量，且麻黄碱的相对减少量多于伪麻黄碱。结论甘草对肺宁合剂中麻黄的有效成分麻黄碱、伪麻黄碱的含量影响明显，反映出了提取过程中甘草麻黄的配伍规律。     

GC-MS analysis of methamphetamine impurities: reactivity of (+)- or (-)-chloroephedrine and cis- or trans-1,2-dimethyl-3-phenylaziridine

S-(+)-Methamphetamine is frequently found as the only isomer in urine specimens from methamphetamine abuseres. Enantiomerically pure S-(+)-methamphetamine can be synthesized from ephedrine or pseudoephedrine via chloroephedrine intermediates. These intermediates are unstable and capable of cyclizing to form cis- and trans-1,2-dimethyl-3-phenyl aziridine. Studies were done to determine if these intermediates could be detected when using a common gas chromatographic-mass spectrometric analytical method (derivatization with heptafluorobutyric anhydride, HFBA) for toxicological screening of methamphetamine. Analysis of (+)- or (-)-chloroephedrine after extraction into hexane and derivatization with HFBA indicated that both pseudoephedrine and ephedrine were the major compounds detected. Direct derivatization of a hexane solution of cis-1,2-dimethyl-3-phenyl aziridine yielded only the derivatives of ephedrine and pseudoephedrine, indicating that the aziridine intermediate is responsible for the formation of the ephedrine or pseudoephedrine. These studies indicate that the aziridine intermediates would not be detected in methamphetamine samples following HFBA derivatization.