HPLC法同时测定复方氨酚烷胺片中咖啡因、马来酸氯苯那敏的含量及含量均匀度

目的建立用高效液相色谱法同时测定复方氨酚烷胺片中咖啡因、马来酸氯苯那敏的含量及含量均匀度。方法色谱柱为Agilent TC-C18(4.6 mm×250 mm,5μm);以乙腈-水-三乙胺(16∶84∶0.5)(用磷酸调节pH值至2.5)为流动相;流速为1.0 mL.min-1;检测波长为262 nm。结果咖啡因和马来酸氯苯那敏分别在0.596 8～2.387 2μg和0.080 1～0.320 3μg范围内与峰面积呈良好线性关系,r值分别为1.000,0.999 9。平均回收率分别为99.7%,99.5%,RSD分别为0.59%,0.68%(n=9)。结论本方法专属性好,简便、快速、准确,适用于复方氨酚烷胺片中咖啡因和马来酸氯苯那敏含量及含量均匀度的测定。     

小儿氨酚黄那敏颗粒中对乙酰氨基酚及马来酸氯苯那敏含量及含量均匀度考察

目的:建立HPLC法测定小儿氨酚黄那敏颗粒中对乙酰氨基酚和马来酸氯苯那敏含量,并考察其含量均匀度。方法:色谱柱:waters C₁₈（150 mm×4.6 mm,5μm）;流动相:甲醇-磷酸二氢钾溶液-三乙胺（15:85:0.02）（磷酸调pH至3.3）;检测波长:215 nn;流速:1.0 ml·min^-1;进样量:10μl。结果:对乙酰氨基酚的线性范围1.000～4.000 mg·ml^-1（r=0.999 7）,平均回收率为101.7%,RSD=1.8%;3批样品的平均含量分别为102.8%,102.4%,103.5%,含量均匀度分别为5.9,5.5,2.7。马来酸氯苯那敏线性范围0.006～0.018 mg·ml^-1（r=0.999 7）,平均回收率为98.7%,RSD=2.0%;3批样品的平均含量分别为100.1%,98.9%,97.9%,含量均匀度分别为4.6,3.9,7.0。结论:测定方法简便,重复性好,精密度高,可以用于小儿氨酚黄那敏颗粒的质量控制。     

Content uniformity studies in tablets by NIR-CI

Near Infrared Chemical Imaging (NIR-CI) is attracting growing interest in pharmaceutical analysis by virtue of its ability to provide a wealth of information from a single sample. Among others, NIR-CI has enabled the determination of the quantitative composition and distribution of acetylsalicylic (ASA) from the analysis of commercial tablets. In this work, we analyzed ASA commercial tablets of four different brands purchased at local chemists. The nominal ASA concentration for the brands was calculated from the nominal content and averaged weight of tablets. The tablets were found to span an ASA concentration range of 71-82%, and to differ in size and composition between brands.The API content and its homogeneity distribution were determined by applying quantitative algorithm to global hyperspectral image of ten tablets. Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) is used to quantify each pixel in the images to obtain appropriate concentration maps. No prior calibration or reference data were needed for quantitation and results are close to the nominal content used as reference. Application to an image for 10 tablets and an individual tablet quantitation of the API allowed us to obtain the Accepted Value (AV) as defined by the European Pharmacopoeia. We conclude that all brands meet the pharmacopoeia specifications.     

Chemometric and derivative methods as flexible spectrophotometric approaches for dissolution and assaying tests in multicomponent tablets

Two derivative spectrophotometric (ratio derivative spectra and algorithm bivariate calibration) and a chemometric methods (partial least squares, PLS) are proposed for the simultaneous determination of binary mixtures in tablet analysis and dissolutions tests, without prior separation. These approaches are successfully applied to quantify trimethoprim (TMP) combined with sulfamethoxazole (SMX) or sulfamethazine (SMZ) or sulfafurazole (SFZ) using the information in the absorption spectra of appropriate solutions. Beer's law was obeyed in the concentration range of 0.98-17.5 microg/ml for TMP, 0.95-17.2 microg/ml for SMX, 1.16-17.5 microg/ml for SMZ and 0.97-17.4 microg/ml for SFZ. The first derivative (1D) bivariate algorithm method involves the use of four calibration curves: two for each compound at two different wavelengths, selected by Kaiser's method. Similarly, the first derivative ratio spectrophotometry employs the linear relationship between the ratio spectra of the analytes and the concentration range. The results were compared with those obtained by PLS multivariate calibration. The calibration models from PLS were pre-treated by orthogonal signal correction and evaluated by cross-validation using the 'SIMCA-P 9' software. Synthetic mixtures of TMP and sulfonamides were used in five different sets for the validity of the calibrations. Mean recoveries for derivative ratio, derivative bivariate and PLS methods were found to be between 99.7% and 102.0% for TMP, 99.4% and 100.2% for SMX, 99.3% and 101.0% for SMZ and 98.1% and 102.3% for SFZ. The calibrations of the three methods were successfully applied to the assaying and dissolution of placebo and commercial tablets without any prior separation. More than 85% of TMP, SMX and SMZ were dissolved within 15 min. For SFZ, only 85% of the compound was dissolved after 60 min. In this study, the three spectrophotometric methods can be satisfactorily used for the quantitative analysis and for dissolution tests of multicomponent dosage forms.     

HPLC法测定感冒灵胶囊5种有效成分的含量

目的建立测定感冒灵胶囊中对乙酰氨基酚、绿原酸、咖啡因、马来酸氯苯那敏和蒙花苷的含量分析方法。方法采用高效液相色谱(HPLC)法,色谱柱为Waters XBridge C 18(4.6 mm×250 mm,5μm);流动相为甲醇-4%冰醋酸(三乙胺调节pH值至3.0);梯度洗脱;绿原酸和蒙花苷检测波长为334 nm,对乙酰氨基酚、马来酸氯苯那敏和咖啡因检测波长为260 nm;流速为1.0 mL·min-1;柱温为35℃。结果对乙酰氨基酚、绿原酸、咖啡因、马来酸氯苯那敏及蒙花苷5个成分在测定的范围内均表现出良好的线性关系(r≥0.9996),平均回收率为98.45%~100.12%。结论该方法操作快速简便,分离效果好,灵敏度高,重现性良好,为测定感冒灵胶囊主成分的含量提供了一种快速高效可靠的方法。     

Simultaneous spectrophotometric determination of mefenamic acid and paracetamol in a pharmaceutical preparation using ratio spectra derivative spectrophotometry and chemometric methods

Four new methods are described for the simultaneous determination of mefenamic acid (MEF) and paracetamol (PAR) in their combination. In the first method, ratio spectra derivative method, analytical signals were measured at the wavelengths corresponding to either maximums or minimums for both drugs in the first derivative spectra of the ratio spectra obtained by dividing the standard spectrum of one of two drugs in 0.1 M NaOH:methanol (1:9). In the chemometric techniques, classical least-squares, inverse least-squares and principal component regression (PCR), the training was randomly prepared by using the different mixture compositions containing two drugs in 0.1 M NaOH:methanol (1:9). The absorbance data was obtained by the measurements at 13 points in the wavelength range 235–355 nm in the absorption spectra. Chemometric calibrations were constructed by the absorbance data and training set for the prediction of the amount of MEF and PAR in samples. In the third chemometric method, PCR, the covariance matrix corresponding to the absorbance data was calculated for the basis vectors and matrix containing the new coordinates. The obtained calibration was used to determine the title drugs in their mixture. Linearity range in all the methods was found to be 2–10 μg/ml of MEF and 4–20 μg/ml of PAR. Mean recoveries were found satisfactory (>99%). The procedures do not require any separation step. These methods were successfully applied to a pharmaceutical formulation, tablet, and the results were compared with each other.     

小儿氨酚黄那敏颗粒中马来酸氯苯那敏含量测定及含量均匀度研究

目的:建立HPLC法测定小儿氨酚黄那敏颗粒中的马来酸氯苯那敏含量的方法并研究其含量均匀度。方法:采用C18柱,甲醇-0.05 mol/L磷酸二氢钠-三乙胺(300∶700∶0.25),用磷酸调节pH值至2.5为流动相,流速为l mL/min,检测波长为264 nm,进样量为20μL。结果:马来酸氯苯那敏的峰面积Y对进样量X(μg)的回归曲线为:Y=7794300X 0.1558;r=0.9996,线性范围为5.56~55.60μg/mL。结论:该方法快速简便,重现性好,适用于小儿氨酚黄那敏颗粒中的马来酸氯苯那敏的质量控制。     

高效液相色谱法测定注射用亚胺培南/西司他丁钠含量及含量均匀度

目的建立高效液相色谱法测定注射用亚胺培南/西司他丁钠的含量及含量均匀度。方法采用CAPCELL PAK C18色谱柱(AQ型,250mm×4.6mm,5μm),流动相为含0.2%己烷磺酸钠的0.001m ol/L磷酸二氢钾溶液(用0.5m ol/L H3PO4调节pH 6.8)∶甲醇(95∶5),流速1.0m l/m in,柱温50℃,检测波长254nm。结果亚胺培南的线性范围为0.120~0.600m g/m l(r=0.9995,n=5),西司他丁的线性范围为0.120~0.600m g/m l(r=0.9999,n=5),平均回收率分别为99.4%(RSD=0.6%),99.7%(RSD=1.0%)。结论本法快速、准确、重现性好,能同时测定制剂中亚胺培南和西司他丁的含量与含量均匀度,还可用于控制该制剂的有关物质。     

HPLC测定复方氨酚烷胺片中的对乙酰氨基酚、咖啡因和马来酸氯苯那敏

目的采用HPLC同时测定复方氨酚烷氨片中对乙酰氨基酚、咖啡因、马来酸氯苯那敏的含量,增加小剂量成分咖啡因、马来酸氯苯那敏含量均匀度检查的方法。方法采用C18柱,流动相为1%醋酸(二乙胺调pH3.7)-甲醇(62∶38),检测波长对乙酰氨基酚用246 nm,咖啡因、马来酸氯苯那敏用262 nm。结果对乙酰氨基酚、咖啡因、马来酸氯苯那敏分别在0.1055～2.11μg(r=0.9999)、0.245～7.35μg(r=0.9997)、0.04216～0.8432μg(r=0.9999)与峰面积有良好的线性关系;平均回收率分别为98.7%、98.6%、101.1%(n=9)。结论所用方法操作简便、准确、重复性好,可用于复方氨酚烷氨片的质量控制。     

Estimation of paracetamol and aceclofenac in tablet formulation by ratio spectra derivative spectroscopy

A new sensitive, simple, rapid and precise method for simultaneous estimation of paracetamol and aceclofenac in combined tablet dosage form has been developed. The method is based on ratio derivative spectrophotometry. The amplitude in first derivative of the ratio spectra at 256 nm and 268 nm (minima) were selected to determine paracetamol and aceclofenac in combined formulation. The method showed good linearity, accuracy and reproducibility. Results of analysis were validated statistically and by recovery studies.     

Validated stability indicating chromatographic method for determination of baricitinib and its degradation products in their tablet dosage form: Implementation to content uniformity and in vitro dissolution studies

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Scheme 1: Graphical Abstract for the proposed method.Schéma 1 : Résumé graphique de la méthode proposée.

     

Ratio spectra derivative spectrophotometry for the determination of furosemide and spironolactone in a capsule formulation

The determination of furosemide and spironolactone in a capsule formulation has been investigated using techniques such as Vierordt's method and derivative spectroscopy dA/d lambda and d2A/d lambda2 applying the zero-crossing technique following reported methods. In our hands, using standard mixtures, these methods gave unreliable results. We have therefore investigated the use of ratio spectra derivative spectrophotometry for this determination. The technique of ratio spectra derivative spectrophotometry was developed in 1990, and has recently been used for a number of analyses of co-formulated products. The method was applied to the analysis of standard mixtures of the two drugs and the combined contents of 20 capsules resulting in values (mean +/- standard deviation) of 102.1 +/- 1.9% and 101.4 +/- 4.0% of the stated content for furosemide and spironolactone, respectively. Similarly, the analysis of individual capsules resulted in values of 101.5 +/- 1.6% and 102.2 +/- 1.4% of the stated content for furosemide and spironolactone, respectively.     

Dissolution testing of acetylsalicylic acid by a channel flow method—correlation to USP basket and intrinsic dissolution methods

A new modification of the channel flow dissolution method is introduced together with the theoretical basis to extract the solubility and mass transfer parameters from the dissolution experiments. Correlation of drug dissolution profiles in the channel flow apparatus was evaluated with respect to USP basket and intrinsic dissolution methods at pH 1.2 or 6.8. Acetylsalicylic acid (ASA) was studied as a pure drug substance and as three simple tablet compositions with microcrystalline cellulose (MCC) and/or lactose as excipients. The channel flow measurements of 100% ASA tablets correlated well with the results of intrinsic dissolution tests. In the channel flow method as well as in the USP basket method the release of ASA was fastest from the tablet compositions containing lactose, while the slowest dissolution rate was observed with the composition containing MCC as the only excipient. As presumed, the dissolution rate of the weak acid was decreased as the pH of the medium was lowered, which was clearly confirmed also by the three dissolution methods. MCC forms matrix tablets and in the USP basket method the dissolution profiles followed square root of time kinetics indicating that diffusion was the rate-controlling step of ASA dissolution. Also the channel flow results indicated that the dissolution of ASA was controlled by mass transfer. The swelling behaviour of the tablets is different in the channel flow method as compared to the basket method: only one tablet surface is exposed to the dissolution medium in the channel flow system. The contact between the tablet surface and the dissolution medium is more similar between the channel flow and intrinsic dissolution methods.     

A comparison of matrix resolution method, ratio spectra derivative spectrophotometry and HPLC method for the determination of thiamine HCl and pyridoxine HCl in pharmaceutical preparation

A comparison of two spectrophotometric methods and a HPLC method were described in this work for the analysis of pyridoxine hydrochloride and thiamine hydrochloride in a vitamin combination. In the first method, A₁¹ (1%, 1 cm) values of these two compounds were calculated using absorbances measured at 246.8 and 290.5 nm in zero-order spectra. The matrix was written for A₁¹ (1%, l cm) values and the concentration of both compounds were determined using ‘Matlab’ software. In the second method, the measurements in the derivative of the ratio spectra were made at 297.8 and 309.5 nm for pyridoxine hydrochloride and at 245.6 and 257.7 nm for thiamine hydrochloride. The calibration graphs were established in the range 8–40 μg/ml of both vitamins. In the HPLC method, the separation of these compounds was realized on a Nucleosil 100-5 C₁₈ column with 0.1 M (NH₄)₂C0₃–water–methanol (5:15:80 v/v) as the mobile phase. Results of spectrophotometric and HPLC procedures were compared.     

Green analytical chromatographic assay method for quantitation of cyclobenzaprine in tablets,spiked human urine and in-vitro dissolution test

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基于层次分析法评分的多指标正交试验法优选宣木瓜的醇水双提工艺

目的 筛选宣木瓜的最佳提取工艺.方法 采用正交试验法,以齐墩果酸和熊果酸、总有机酸、总多酚和总多糖提取量为指标;层次分析法确定权重,多指标综合评分优选宣木瓜醇水双提的工艺参数.结果 最佳提取工艺为:8倍量75％乙醇回流提取2次,每次2h,药渣再用12倍量水回流提取2h.结论 优选工艺为宣木瓜提取物及配方颗粒制备奠定了基础.     

An eco-friendly HPLC-UV method for the determination of risedronate in its bulk and tablet dosage form with application to content uniformity,dissolution and stability testing

Risedronate is a nitrogen-containing bisphosphonate for the treatment and prevention of postmenopausal osteoporosis. The current work aims to develop a novel green HPLC-UV method for the rapid analysis of risedronate sodium in bulk and tablet formulation. The analyzed samples were separated on Waters Atlantis dC18 (150 mm × 3.9 mm; 5 μm) column using a green mobile phase consisting of potassium phosphate buffer pH 2.9 and potassium edetate buffer pH 9.5 in a ratio of 1:2, the final pH was adjusted to 6.8 with phosphoric acid, the mobile phase was pumped at a rate of 1.0 mL/min, with column temperature set at 30 °C, eluted samples were detected at 263 nm and the chromatographic run time was 3.0 min. The method was found to be linear over the concentration range of 14–140 μg/mL with a correlation coefficient (r²) of 0.9994. Accuracy and precision were evaluated from three QC samples (LQC, MQC and HQC) together with the five calibrators where the percentage accuracy was found to be 101.84%. Processed quality control samples of risedronate sodium were tested for stability at different conditions, short term, long term and freeze- thaw stability. The current method was further extended to study the content uniformity of Actonel® tablets following United States Pharmacopoeia (USP) guidelines. The proposed method was fully validated as per ICH guidelines.