HPLC法测定复方愈酚麻黄糖浆中愈创甘油醚和马来酸氯苯那敏

目的：建立测定复方愈酚麻黄糖浆中愈创甘油醚和马来酸氯苯那敏含量的高效液相色谱法（HPLC）。方法: 色谱柱为Agilent SB-C18柱（4.6mm×250 mm,5?m）,流动相：乙腈- 0.02 mol?L-1磷酸二氢钾（含0.1%三乙胺,用磷酸pH至3.0）（25:75）,检测波长：260nm,流速1.0mL?min-1,柱温：25℃。结果：愈创甘油醚在0.0120～1.2035?g范围内线性关系良好,回归方程Y=296882X+31351（R2=0.9998）,方法回收率在99.50～ 102.82%之间（RSD在0.06～0.41%之间）（n=9）,13批样品的愈创甘油醚含量在98.23～102.84%之间;马来酸氯苯那敏在0.0061～0.6055?g范围内线性关系良好,回归方程Y=752335x-921.9（R2=1.0000）,方法回收率在97.70～ 98.46%之间（RSD在0.32～0.64%之间）（n=9）,13批样品的马来酸氯苯那敏含量在92.39～101.22%之间;结论：该方法简便,快速,准确,可用于该制剂中愈创甘油醚和马来酸氯苯那敏的含量测定。     

Simultaneous determination of dextromethorphan, dextrorphan, and guaifenesin in human plasma using semi-automated liquid/liquid extraction and gradient liquid chromatography tandem mass spectrometry

A method for the simultaneous determination of dextromethorphan (DEX), dextrorphan (DET), and guaifenesin (GG) in human plasma was developed, validated, and applied to determine plasma concentrations of these compounds in samples from six clinical pharmacokinetic (PK) studies. Semi-automated liquid handling systems were used to perform the majority of the sample manipulation including liquid/liquid extraction (LLE) of the analytes from human plasma. Stable-isotope-labeled analogues were utilized as internal standards (ISTDs) for each analyte to facilitate accurate and precise quantification. Extracts were analyzed using gradient liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Use of semi-automated LLE with LC-MS/MS proved to be a very rugged and reliable approach for analysis of more than 6200 clinical study samples. The lower limit of quantification was validated at 0.010, 0.010, and 1.0 ng/mL of plasma for DEX, DET, and GG, respectively. Accuracy and precision of quality control (QC) samples for all three analytes met FDA Guidance criteria of +/-15% for average QC accuracy with coefficients of variation less than 15%. Data from the thorough evaluation of the method during development, validation, and application are presented to characterize selectivity, linearity, over-range sample analysis, accuracy, precision, autosampler carry-over, ruggedness, extraction efficiency, ionization suppression, and stability. Pharmacokinetic data are also provided to illustrate improvements in systemic drug and metabolite concentration-time profiles that were achieved by formulation optimization.     

A new technique for spectrophotometric determination of pseudoephedrine and guaifenesin in syrup and synthetic mixture

The accuracy in predicting different chemometric methods was compared when applied on ordinary UV spectra and first order derivative spectra. Principal component regression (PCR) and partial least squares with one dependent variable (PLS1) and two dependent variables (PLS2) were applied on spectral data of pharmaceutical formula containing pseudoephedrine (PDP) and guaifenesin (GFN). The ability to derivative in resolved overlapping spectra chloropheniramine maleate was evaluated when multivariate methods are adopted for analysis of two component mixtures without using any chemical pretreatment. The chemometrics models were tested on an external validation dataset and finally applied to the analysis of pharmaceuticals. Significant advantages were found in analysis of the real samples when the calibration models from derivative spectra were used. It should also be mentioned that the proposed method is a simple and rapid way requiring no preliminary separation steps and can be used easily for the analysis of these compounds, especially in quality control laboratories.     

Microencapsulation of a hydrophilic drug into a hydrophobic matrix using a salting-out procedure. I: Development and optimization of the process using factorial design

The congealable disperse phase method for preparing sustained release microspheres involves an emulsification process using water as the external phase and molten hydrophobic wax as the disperse phase into which the drug is loaded. Attempts to entrap highly water-soluble drugs using this process have often resulted in low loading efficiency as the drugs partition into the external water phase during emulsification and are lost. A novel method employing salts and wetting agents was developed to improve the loading efficiency of the highly water-soluble drug, guaifenesin, using this method. The drug/wax ratio (D/W) and the presence of salts and wetting agents greatly influenced microsphere properties. To optimize the process for drug loading efficiency and release rate, three different D/Ws, salts and wetting agents were chosen and a full 3³ factorial design experiment was performed. Any significant differences among the levels of the variables and their individual and joint effects on entrapment efficiency and T₅₀ (time for 50% drug release) were determined. Entrapment efficiencies in the range 35.1-86.3% were obtained for the various factor-level combinations of the variables. Particle size was in the range 140-385 µm and T₅₀ was 0.59-2.72 h for the microspheres obtained. The D/W and type of salt used significantly affected drug entrapment and T₅₀, while the nature of wetting agent was not significant at p < 0.05. The microspheres prepared using 1:4 D/W showed the highest entrapment efficiency and slowest drug release.     

愈创甘油醚双层缓释片与普通片在犬体内药动学的比较研究

目的:比较愈创甘油醚双层缓释片与普通片在犬体內药动学特征。方法:Beagle犬单剂量给予600mg愈创甘油醚双层缓释片或愈创甘油醚普通片后,用RP-HPLC法测定犬血浆中愈创甘油醚的药物浓度,计算药动学参数和相对生物利用度。结果:Beagle犬单剂量口服给药后,受试制剂和参比制剂中愈创甘油醚的AUC_0-12h分别为（15.96±6.41）μg·h·ml^-1和（19.23±4.96）μg·h·ml^-1;C_max分别为（7.31±2.86）μg·ml^-1和（14.24±5.34）μg·ml^-1;t_max分别为（0.79±0.25）h和（1.08±0.38）h;t_1/2分别为（2.50±1.67）h和（0.42±0.05）h;MRT_0-1分别为（2.37±0.61）h和（1.42±0.30）h。结论:愈创甘油醚双层缓释片的C_max较普通片显著降低,MRT_0-1和t_1/2明显延长,差异有统计学意义（P<0.05）,说明该受试制剂具备一定的缓释药动学特征。     

LC/MS/MS法测定人血浆中愈创木酚甘油醚浓度及药动学研究

目的:建立以高效液相色谱-质谱联用法测定人血浆中愈创木酚甘油醚浓度的方法,并研究愈创木酚甘油醚片的人体药动学。方法:碱化的血浆药品经乙酸乙酯萃取后,以甲醇-1%甲酸(70:30)为流动相,对乙酰氨基酚为内标,采用Aquasil C18柱分离。通过液相色谱-串联质谱联用仪,以选择反应监测方式进行检测,定量分析的离子反应分别为m/z199→m/z125(愈创木酚甘油醚)和m/z152→m/z110(对乙酰氨基酚)。结果:愈创木酚甘油醚检测浓度在5·0～2500ng·mL-1范围内线性关系良好(r=0·9953),定量下限为5·0ng·mL-1。20名受试者口服愈创木酚甘油醚片0·2g后的主要药动学参数Cmax为(754·6±190·5)ng·mL-1、t1/2为(0·97±0·12)h、tmax为(0·63±0·22)h、AUC0～t为(1435·8±441·9)ng·h·mL-1、AUC0～∞为(1444·9±449·3)ng·h·mL-1。结论:本方法简便、快速、灵敏,可用于愈创木酚甘油醚的临床药动学研究。     

Pseudoephedrine and guaifenesin urolithiasis: widening the differential diagnosis of radiolucent calculi on abdominal radiograph

Unenhanced helical computed tomography has played an increasingly important role in the management of urinary tract stones, guiding diagnosis and control of calculus disease. We report computed tomographic and radiographic appearances of a renal calculus composed of pseudoephedrine and guaifenesin in a patient who abused over-the-counter allergy medication.     

反相高效液相色谱法测定镇祛平口服液3种主要成分的含量

目的采用反相高效液相色谱法测定镇祛平口服液中盐酸曲普利定(C)、愈创甘油醚(G)和氢溴酸右美沙芬(D)3种主要成分的含量。方法色谱柱：YWG C18柱(150 mm×5 mm，10 μm)；流动相：770 mL甲醇 230 mL重蒸纯化水(含5 mmol·L 1庚烷磺酸钠，用磷酸调pH值为30)；在波长262 nm处进行检测。结果C在8594～77786 μg·mL 1，G在1888 ～1 6988 μg·mL 1，D在4108～36972 μg·mL 1浓度范围内线性关系良好。C的回收率＝ 999%，RSD＝080%；G的回收率＝1016%，RSD为069%；D的回收率＝1005%，RSD为068%。结论该法简便、快速、准确，可用于镇祛平口服液中3种主要成分的含量测定。     

Green chromatographic method for analysis of some anti-cough drugs and their toxic impurities with comparison to conventional methods

Toxic solvents are widely used in chemical laboratories, which are dangerous on health, safety of workers, and environment. Green chemistry established different principles to keep safety of environment, one of these goals is to replace toxic solvents by greener alternatives or by minimizing the used volumes.Paracetamol (PAR), Guaifenesin (GUF), Oxomemazine (OX), and Sodium benzoate (SB) combination is a widely used cough preparation. 4- aminophenol (4-AP) is PAR poisonous impurity and related substance. Guiacol (GUC) is GUF impurity and related substance; its presence may lead to rejection of GUF sample.An eco-friendly HPTLC method was developed to quantify the studied drugs and their impurities. Chromatographic separation was achieved on HPTLC 60F254 plates using ethylacetate: methanol: 0.05?M ammonium chloride buffer (100: 2: 5, by volume) as a mobile phase and scanning at 225?nm. The linear ranges were 0.25–3.50, 0.50–8.00, 0.25–4.00, 0.20–8.00, 0.05–4.00, and 0.25–4.00?µg/band for PAR, GUF, OX and SB, 4-AP, and GUC. Method was successfully applied to available syrup and suppositories. It compared well with the reported method. It can be considered as an alternative green method for previously developed TLC method. Greenness profile of the method proved that it is greener than the reported methods being time and solvents saving.     

RP-HPLC-UV method development and validation for simultaneous determination of terbutaline sulphate,ambroxol HCl and guaifenesin in pure and dosage forms

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