Drugs In Pharmaceutical Preparations Research Articles

Simultaneous determination of miconazole and hydrocortisone or mometasone using reversed phase liquid chromatography

Two simple, rapid and precise reversed phase liquid chromatographic methods have been developed and validated for the simultaneous determination of miconazole nitrate in two binary mixtures, with hydrocortisone acetate (Mixture 1) and mometasone furoate (Mixture 2). For the two mixtures, chromatographic separation was carried out on a C18 column. For mixture 1, a mobile phase consisting of 2.22 mM sodium dihydrogen phosphate (Triethylamine 0.2%):acetonitrile (45:55, v : v ) at a flow rate of 0.9 mL/min was used at ambient temperature. Quantitative determination of miconazole and hydrocortisone was achieved with UV detection at 215 and 245 nm, respectively. Linearity, accuracy and precision were found to be acceptable over the concentration range of 30-80 μg/mL for miconazole and 4-80 μg/mL for hydrocotisone. For mixture 2, a mobile phase consisting of acetonitrile:water (Triethylamine 0.2%) (70:30, v : v ) at a flow rate of 0.9 mL/min was used at ambient temperature. Quantitative determinations of miconazole and mometasone were achieved with UV detection at 215 and 250 nm, respectively. Linearity, accuracy and precision were found to be acceptable over the concentration range of 10-200 μg/mL for miconazole and 2-60 μg/mL for mometasone. The optimized methods were proved to be specific, robust and accurate for the quality control of the cited drugs in pharmaceutical preparations.

Development and application of stability-indicating HPLC method for the determination of nevirapine and its impurity in combination drug product

Summary A stability-indicating reversed-phase high-performance liquid chromatography method has been developed and validated for the estimation of nevirapine and its impurity, namely the related compound A and the related compound B in combination drug product. The separation was carried out on SUPELCOSIL ABZ (150 mm × 4.6 mm, 5 µm) column. Tablet was admitted to the stress conditions of acid, base, peroxide, thermal, humidity, and photolytic degradation. The degradation products were well resolved from nevirapine, and its impurities peaks and the peak homogeneity of compound were obtained using photo diode array detector, hence proving the stability-indicating nature of the method. Moreover, to prove the selectivity of the method, individual lamivudine, zidovudine, and their main impurities were injected. The developed method was linear for nevirapine from 120 to 360 µg mL−1, and the linear regression obtained was >0.999. Recovery data were in the range 98.2–101.5%. The limit of quantification for related compound A and related compound B was found to be 0.02%. The proposed method was validated according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines and proved suitable for stability testing and quality control of these drugs in pharmaceutical preparations.

GC Determination of Famotidine, Ranitidine, Cimetidine, and Metformin in Pharmaceutical Preparations and Serum Using Methylglyoxal as Derivatizing Reagent

A capillary gas chromatography (GC) procedure has been developed for the determination of four pharmaceutical preparations (famotidine, ranitidine, cimetidine, and metformin) after precolumn derivatization with methylglyoxal (MGo). GC was carried out using an HP-5 column (30 m × 0.32 mm id) at an initial column temperature of 90 °C for 2 min, followed by heating rate of 25 °C min−1 up to 265 °C. Nitrogen flow rate was 2.5 mL min−1 with split ratio 10:1. A linear calibration curve was obtained within 50–1,000 ng mL−1 and the limit of detection (LOD) was within 17–25 ng mL−1. The derivatization, GC elution, and separation were repeatable in terms of retention time and peak height/peak area with relative standard deviation within ±4.6 %. The procedure was applied to the determination of the drugs in pharmaceutical preparations and the sera of volunteers who were given oral doses of the drugs. The results of the analysis agreed with the labeled values of the pharmaceutical preparations and were 147–4,903 ng mL−1 in serum with an RSD within 1.0–4.2 %, after ingestion of a single dose of 40–500 mg of active ingredient in a tablet.

Simultaneous Determination of Metformin, Nateglinide and Gliclazide in Pharmaceutical Preparations Using Micellar Liquid Chromatography

A micellar chromatographic method has been developed and validated for simultaneous separation and determination of metformin(MF), nateglinide (NT) and gliclazide (GL) . The separation was carried out using a Nucleosil C18 column, 150 mm × 4.6 mm i.d., 5 µm particle size, using micellar mobile phase consisting of sodium dodecyl sulphate (SDS), n-propanol with UV detection. The optimum conditions for the simultaneous separation of the three drugs were 0.12 M SDS, 10% (v/v) n-popanol, 0.3% triethylamine adjusted to pH5.6 with a flow rate of 1 ml.min-1 and detection at 254 nm. The limit of detection (LOD) of MF, NT, GL were 0.047, 0.00115, 0.036 µg.mL-1 respectively. The method showed good linearity in the ranges of 0.4-16 µg.mL-1, (r2=0.999), 0.8-16 μg.ml-1 (r2=0.999) and 1-40 μg.ml-1 (r2=0.999) for MF, NT, GL respectively. The suggested method was successfully applied for the analysis of the three antidiabetic drugs in pharmaceutical preparations with average recoveries of 99.66%, 100.08% and 100.31% for MT, NT and GL respectively. The results obtained were in good agreement with those obtained from comparison methods. The method was validated regarding accuracy and precision.

DEVELOPMENT AND VALIDATION OF A NOVEL RP-HPLC METHOD FOR SIMULTANEOUS DETERMINATION OF SALBUTAMOL SULFATE, GUAIFENESIN, AND AMBROXOL HYDROCHLORIDE IN TABLET FORMULATION

A simple and precise liquid chromatography method for the simultaneous estimation of Salbutamol sulfate, Guaifenesin, and Ambroxol hydrochloride in combined tablet dosage form was developed and validated. The chromatographic separation of the drugs was achieved with a Princeton sphere C-8 25 cm × 4.6 mm (Rankem) analytical column using buffer and methanol (58:42 v/v) as the mobile phase. The buffer used in mobile phase contained 0.1 M potassium dihydrogen phosphate and its pH was adjusted to 4.5 with 10% ortho-phosphoric acid. The instrument was set at a flow rate of 1.0 mL min−1, column at ambient temperature, and the wavelength of UV-visible detector at 220 nm. The method showed excellent linearity over a range of 5–35 µg mL−1 for all the drugs. The correlation coefficients for Salbutamol sulfate, Guaifenesin, and Ambroxol hydrochloride were noted to be 0.9998, 0.9998, and 0.9995, respectively, and the mean recovery values were found to be 99.53%, 100.28%, and 100.05%, respectively. The proposed method could be suitable for quantitative determination of these drugs in pharmaceutical preparations and also for quality control in bulk manufacturing. The intermediate precision data was subjected to statistical analysis (F-test and t-test at 95% confidence level).

Chemometrics in Pharmaceutical Analysis: An Introduction, Review, and Future Perspectives

Chemometrics is the application of statistical and mathematical methods to analytical data to permit maximum collection and extraction of useful information. The utility of chemometric techniques as tools enabling multidimensional calibration of selected spectroscopic, electrochemical, and chromatographic methods is demonstrated. Application of this approach mainly for interpretation of UV-Vis and near-IR (NIR) spectra, as well as for data obtained by other instrumental methods, makes identification and quantitative analysis of active substances in complex mixtures possible, especially in the analysis of pharmaceutical preparations present in the market. Such analytical work is carried out by the use of advanced chemical instruments and data processing, which has led to a need for advanced methods to design experiments, calibrate instruments, and analyze the resulting data. The purpose of this review is to describe various chemometric methods in combination with UV-Vis spectrophotometry, NIR spectroscopy, fluorescence spectroscopy, electroanalysis, chromatographic separation, and flow-injection analysis for the analysis of drugs in pharmaceutical preparations. Theoretical and practical aspects are described with pharmaceutical examples of chemometric applications. This review will concentrate on gaining an understanding of how chemometrics can be useful in the modern analytical laboratory. A selection of the most challenging problems faced in pharmaceutical analysis is presented, the potential for chemometrics is considered, and some consequent implications for utilization are discussed. The reader can refer to the citations wherever appropriate.

Potentiometric Membrane Sensors for Determination of Memantine Hydrochloride and Pramipexole Dihydrochloride Monohydrate

Five solid membrane sensors responsive to memantine hydrochloride (MEM) and pramipexole dihydrochloride monohydrate (PXL) are described for simple and fast determination of these drugs in pharmaceutical preparation and human plasma. The first and the second sensors are based on the formation of an ion association complex between MEM as a cationic drug with Na tetra phenyl borate and ammonium reineckate (as anionic exchanger), respectively. The third sensor is based on the formation of an ion association complex between PXL with ammonium reineckate. The produced electroactive material is dispersed in PVC matrix. While the other fourth and fifth sensors are based on using functionalized lipophilic cyclodextrin derivative (2-hydroxypropyl-�-cyclodextrin) as sensor ionophore for the determination of MEM and PXL. The performance characteristics of these sensors-evaluated according to IUPAC recommendations-reveal fast, stable and near Nernstian response for 1x10 -4 -1x10 -1 M and 1x10 -6 -1x10 -2 M for (MEM) and (PXL), respectively. Many inorganic and organic substances such as drug excipients and diluents normally used in drug formulations do not interfere with drugs response. Statistical comparison between the results obtained by applying the proposed potentiometric method for the determination of the (MEM) and (PXL) in their pure powder forms and those obtained by applying the reported methods was done and no significant difference was found at p =0.05. Validation of the method according to ICH guidelines shows the suitability of the sensors for quality control analysis of the cited drugs in pharmaceutical formulations and human plasma. The proposed sensors can also be used as a detector for HPLC.

Validated Stability-Indicating Reversed-Phase-HPLC Method for Simultaneous Determination of Orphenadrine Citrate, Caffeine and Aspirin

New, simple, rapid and precise reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of orphenadrine citrate, caffeine and aspirin in presence of aspirin degradation products, orphenadrine citrate and caffeine process related impurities, and excipients. Good resolution and quantization were achieved on reversed-phase column [Phenomenex™ Luna ODS C(18) (25 cm×4.6 mm, 5 µm particles)]. Gradient elution based on; eluant [A]: 0.1% triethylamine in aqueous potassium dihydrogen phosphate buffer (50 mM; pH 3.0), while as, eluant [B]: acetonitrile, at a flow rate of 1.5 mL min(-1). UV quantitation was set at 215 nm. Linearity was exhibited for orphenadrine citrate, caffeine and aspirin within 0.5-150, 0.5-360 or 0.7-301 µg mL(-1) ranges, respectively. Satisfactory validation results were ascertained in terms of low limits of quantiation (6.33×10(-2)-7.94×10(-2)), mean percentage recovery (98.9-101.4%), precision (<2%) and robustness. The proposed method was proved to be specific, robust and accurate for the determination of cited drugs in pharmaceutical preparations in presence of their degradation products.

Bioavailability study of triamterene and xipamide using urinary pharmacokinetic data following single oral dose of each drug or their combination

An efficient chromatographic method for the simultaneous determination of triamterene (TRI) and xipamide (XIP) in urine samples, based on high performance liquid chromatography with photodiode array detector (HPLC–DAD) has been developed. The HPLC separation was performed on a RP stainless-steel C-18 analytical column (250 mm × 4.6 mm, 5 μm) with a gradient elution system of 0.05 M phosphate buffer adjusted to pH 4.0 and methanol as the mobile phase. The method was used to determine the urinary excretion profile and to calculate different urinary pharmacokinetic parameters following oral dose of their combination compared with single oral doses of each drug and hence comparing their bioavailability. Quantitation was performed using chlorthalidone as internal standard. The calibration graphs of each drug were rectilinear in the range of 0.2–40 μg/mL urine for TRI and 0.2–15 μg/mL urine for XIP. An HPLC–DAD method was also successfully developed for the simultaneous determination of the investigated drugs in pharmaceutical preparations. The methods were validated in terms of linearity, accuracy, precision, selectivity, limits of detection and quantitation and other aspects of analytical validation.

Validated Spectroflurimetric Determination of Some H1 Receptor Antagonist Drugs in Pharmaceutical Preparations Through Charge Transfer Complexation

A validated simple, rapid, and selective spectrofluorimetric method was developed for the determination of some antihistaminic H(1) receptor antagonist drugs namely ebastine (EBS), cetirizine dihydrochloride (CTZ), and fexofenadine hydrochloride (FXD). The method is based on the reaction of the cited drugs with some Π acceptors namely p-chloranilic acid (CLA), tetracyanoethylene (TCNE), and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) to give highly fluorescent derivatives. The fluorescence intensity-concentration plots were rectilinear over the concentration ranges of 0.2-3.0, 0.2-2.5 and 0.15-2.0μg/ml for EBS with CLA, DDQ, and TCNE respectively; 0.5-7.0, 0.5-6.0, and 0.2-4.0μg/ml for CTZ with the previously mentioned reagents, and 0.2-3.5, 0.5-6.0, and 0.2-3.5μg/ml for FXD. The factors affecting the formation of the reaction products were carefully studied and optimized. The method was applied for the determination of the studied drugs in their dosage forms. The results obtained were in good agreement with those obtained by the comparison methods. Reactions Stoichiometries of the complexes formed between the studied drugs and Π acceptors were defined by the Job's method of the continuous variation and found in 1:1 in all cases.

Ionic liquid sensitized fluorescence determination of four isoquinoline alkaloids

The fluorescence spectra of berberine, palmatine, jatrorrhizine, and coptisine in ionic liquids were studied and found to increase significantly in ionic liquids, with [C8MIM][PF6] having the greatest increase. Further studies showed that these drugs could be extracted from an aqueous solution by [C8MIM][PF6] using the temperature-assisted ionic liquid dispersive liquid phase microextraction method. The enrichment factors were 81.8–82.3, and the extraction recovery was 98.5%, 98.1%, 98.3%, and 98.8% for berberine, palmatine, jatrorrhizine, and coptisine, respectively. Based on the [C8MIM][PF6] preconcentration, separation, and sensitized fluorescence for these drugs, a new selective and sensitive method for the determination of concentration of these four drugs in aqueous samples was presented. At optimum conditions, the linear relationship was obtained in the ranges of 0.8–130ngmL−1, 0.9–160ngmL−1, 0.7–140ngmL−1, and 0.6–110ngmL−1, respectively. The proposed method was successfully applied for the determination of the drugs in pharmaceutical preparations, urine, and plasma samples.

Liquid chromatographic determination of sitagliptin either alone or in ternary mixture with metformin and sitagliptin degradation product

Two reversed-phase liquid chromatographic (RP-LC) methods have been developed for the determination of sitagliptin phosphate monohydrate (STG). The first method comprised the determination of STG alone in bulk and plasma; and in its pharmaceutical preparation. This method was based on isocratic elution of STG using a mobile phase consisting of potassium dihydrogen phosphate buffer pH (7.8)–acetonitrile (70:30, v/v) at a flow rate of 1mLmin−1 with flourometric detection. The flourometric detector was operated at 267nm for excitation and 575nm for emission. In the second method, the simultaneous determination of STG and metformin (MET) in the presence of sitagliptin alkaline degradation product (SDP) has been developed. In this method, the ternary mixture of STG, MET and SDP was separated using a mobile phase consisting of potassium dihydrogen phosphate buffer pH (4.6)–acetonitrile–methanol (30:50:20, v/v/v) at a flow rate of 1mLmin−1 with UV detection at 220nm. Chromatographic separation in the two methods was achieved on a Symmetry® Waters C18 column (150mm×4.6mm, 5μm). Linearity, accuracy and precision were found to be acceptable over the concentration ranges of 0.25–200μgmL−1 for STG with the first method and 5–160μgmL−1, 25–800μgmL−1 for STG and MET, respectively with the second method. The optimized methods were validated and proved to be specific, robust and accurate for the quality control of the cited drugs in pharmaceutical preparations.

The determination of phenothiazine drugs in pharmaceutical preparations by a difference spectrophotometric method.

A method is described for the rapid determination of phenothiazine drugs in a wide variety of pharmaceutical preparations. The drugs are determined by a difference spectrophotometric technique based upon the absorbance of the sulphoxide derivative of the drug relative to the absorbance of a solution of the underivatized drug. The sulphoxide derivatives are formed rapidly and quantitatively at room temperature by the addition of a solution of peroxyacetic acid, prepared by the slow reaction of hydrogen peroxide and glacial acetic acid on standing. The difference absorbance of the solutions is proportional to the concentration of the phenothiazine drug in the preparation and is specific for the intact drug in the presence of oxidative and photochemical decomposition products, colouring and flavouring agents, excipients and most co-formulated drugs.

A note on the colorimetric determination of butyrophenones with 3,5-dinitrobenzoic acid.

Abstract Butyrophenones react with 3,5-dinitrobenzoic acid in an alkaline medium with the formation of a red coloured complex. This reaction can be used for the quantitative determination of these drugs in pharmaceutical preparations. The influence of the ethanol concentration, the alkalinity and the reagent concentration was investigated separately. The results show that the proposed method is suitable for the assay of solutions and tablets. It requires less time than existing methods.

Sensitive Extractive Spectrophotometric Method for the Determination of Some Statin Drugs in Pharmaceutical Preparations

Sensitive Extractive Spectrophotometric Method for the Determination of Some Statin Drugs in Pharmaceutical Preparations

Reversed-Phase Ion-Pair HPLC and TLC-Densitometric Methods for the Simultaneous Determination of Ciprofloxacin Hydrochloride and Metronidazole in Tablets

Two methods are described for the simultaneous determination of ciprofloxacin HCl (CIP) and metronidazole (MET) in binary mixture. The first method was based on the ion-pair liquid chromatographic separation of the two drugs on reversed-phase, μBondapak C18 column (250 mm × 4.6 mm, 10 μm) Waters. The mobile phase consisted of monobasic potassium phosphate (50 mM, pH 3, adjusted with phosphoric acid) and acetonitrile (65:35, v/v) containing sodium octane sulphonate (50 mM). Flow rate of 1.2 mL min−1 was applied. Quantitation was achieved with UV detection at 280 nm. Linearity, accuracy and precision were found to be acceptable over the concentration range of 3–180 and 15–180 μg mL−1 for CIP and MET, respectively. The second method was based on the TLC separation of the two drugs followed by densitometric measurements of their bands at 280 nm. The separation was carried out on silica gel 60 F254 plates, using acetonitrile, ammonia, methanol, methylene chloride and hexane (1.3:1.1:2.0:3.0:1.0, v/v) as developing system. The linear regression analysis data were used for the regression line in the range of 1.5–10 μg band−1 for CIP and MET. The two proposed methods were successfully applied to the determination of both drugs in laboratory prepared mixtures and in commercial tablets. The optimized methods proved to be specific, robust and accurate for the quality control of the cited drugs in pharmaceutical preparation.

SIMULTANEOUS ESTIMATION OF PIOGLITAZONE, GLIMEPIRIDE AND GLIMEPIRIDE IMPURITIES IN COMBINATION DRUG PRODUCT BY A VALIDATED STABILITY- INDICATING RP-HPLC METHOD

A new, single, stability indicating RP-HPLC method has been developed and validated for the simultaneous estimation of pioglitazone, glimepiride and glimepiride impurities i.e., related compound B and related compound C from combination drug product containing pioglitazone, glimepiride and metformin HCl. The chromatographic separation was achieved on a cyano stationary phase (250 x 4.6mm, 5.0 microns particles) with simple mobile phase combination delivered in gradient mode at a flow rate of 0.8mL min -1 at 230nm. In the developed method, the critical close eluting compound of glimepiride related compound B and related compound C was found more than 6.5 resolutions. This method is capable to detect glimepiride related compound B and related compound C at a level below 0.005% with respect to glimepiride sample concentration of 0.1mg mL-1 for a 25 µL injection volume. The proposed method was validated according to the ICH guidelines and proved suitable for routine and stability analysis of these drugs in pharmaceutical preparations.

Stripping Voltammetric Determination of Timolol Drug in Pharmaceuticals and Biological Fluids

A sensitive and reliable stripping voltammetric method was developed to determine timolol drug. This method is based on the adsorptive accumulation of the drug at a hanging mercury drop electrode (HMDE) and then a negative sweep was initiated, which yield a well defined cathodic peak at –850 mV versus (Ag/AgCl) silver reference electrode. To achieve high sensitivity, various experimental and instrumental variables were investigated such as supporting electrolyte, pH, accumulation time and potential, scan rate, frequency, pulse amplitude, convection rate and working electrode area. The monitored adsorptive current was directly proportional to the concentration of timolol and it shows a linear response in the range from 1 × 10–7 to 1.5 × 10–6 mol●l–1 of this drug (correlation coefficient = 0.998) and the detection limit (S/N = 3) is 1.26 × 10–9 mol●l–1 at an accumulation time of 30 sec. The developed adsorptive stripping voltammetry (AdSV) procedure shows a good reproducibility, the relative standard deviation RSD% (n = 8) at a concentration level of 1 × 10–6 mol●l–1 of timolol was 0.13%, whereas the method accuracy was indicated via the mean recovery of 110% ± 1.414%. Possible interferences by several substances usually present in the pharmaceutical formulations have been also evaluated. The applicability of this approach was illustrated by the determination of the drug in pharmaceutical preparation and biological fluids such as serum and urine.

Spectrophotometric and spectrofluorimetric determination of some drugs containing secondary amino group in bulk drug and dosage forms via derivatization with 7-Chloro-4-Nitrobenzofurazon

Sensitive and selective spectrophotometric and spectrofluorimetric methods have been developed for determination of some drugs such as Pramipexole, Nebivolol, Carvedilol, and Eletriptan, which commonly contain secondary amino group. The subject methods were developed via derivatization of the secondary amino groups with 7-Chloro-4-Nitrobenzofurazon in borate buffer where a yellow colored reaction product was obtained and measured spectrophotometrically or spectrofluorimetrically. Concentration ranges were found as 2.0 to 250 μg mL-1 and 0.1 to 3.0 μg mL-1, for spectrophotometric and spectrofluorimetric study, respectively. The described methods can be easily applied by the quality control laboratories in routine analyses of these drugs in pharmaceutical preparations.

Simultaneous determination of diclofenac potassium and methocarbamol in ternary mixture with guaifenesin by reversed phase liquid chromatography

New, simple, rapid and precise reversed phase liquid chromatographic (RP-LC) method has been developed for the simultaneous determination of diclofenac potassium (DP) and methocarbamol (MT) in ternary mixture with guaifenesin (GF), degradation product of methocarbamol. Chromatographic separation was achieved on a Symmetry ® Waters C18 column (150 mm × 4.6 mm, 5 μm). Gradient elution based on phosphate buffer pH (8)-acetonitrile at a flow rate of 1 mL min −1 was applied. The UV detector was operated at 282 nm for DP and 274 nm for MT and GF. Linearity, accuracy and precision were found to be acceptable over the concentration ranges of 0.05–16, 0.5–160 and 0.5–160 μg mL −1 for DP, MT and GF, respectively. The optimized method proved to be specific, robust and accurate for the quality control of the cited drugs in pharmaceutical preparation.