Determination Of Ranitidine Research Articles

A novel gradient HPLC method for simultaneous determination of ranitidine, methylparaben and propylparaben in oral liquid pharmaceutical formulation

A selective and accurate high-performance liquid chromatographic method has been developed and validated for the simultaneous determination of ranitidine, methylparaben (MP) and propylparaben (PP) in oral liquids. Samples were purified by solid-phase extraction (SPE) using a copolymeric [poly(divinylbenzene-co- N-vinylpyrrolidone)] sorbent. The chromatographic separation was achieved by HPLC using a mixture of ammonium acetate solution (0.5 M), acetonitrile and methanol as the mobile phase with gradient elution, a Nucleosil C18 column and UV detection at 254 nm. The method was validated with respect to linearity, precision, accuracy, selectivity, and robustness. All the parameters examined met the current recommendations for bioanalytical method validation. The method was found to be applicable to routine analysis (assays and stability tests) of active compound (ranitidine) and preservatives (MP and PP).

Simultaneous determination of ranitidine and metronidazole in human plasma using high performance liquid chromatography with diode array detection

The development and validation of a simple method for the simultaneous determination of ranitidine and metronidazole in human plasma is described. Plasma samples (250 μL) were deproteinized by precipitation with 60% perchloric acid, centrifuged and the supernatant directly injected into the HPLC. Separation was achieved in isocratic mode with a Shimpak C 18 column and a mobile phase consisting of 10 mM potassium dihydrogen phosphate pH 3.5:acetonitrile (90:10, v/v) with UV detection at 315 nm. The method showed good selectivity and sensitivity. Good and consistent recovery for metronidazole and ranitidine was obtained: 96.22 ± 3.52 and 95.00 ± 4.50% for ranitidine (25–1000 ng/mL) and metronidazole (60–10,000 ng/mL), respectively ( n = 3). With this one-step sample preparation method, both ranitidine and metronidazole could be quantified simultaneously in human plasma with good precision (R.S.D. < 15%) and accuracy (bias values below 15%). The limit of quantification for ranitidine and metronidazole were 20 and 40 ng/mL plasma, respectively.

Kinetic Spectrophotometric Determination of Ranitidine

AbstractTwo spectrophotometric methods were developed for the determination of ranitidine. The first method was a kinetic spectrophotometric method based on the catalytic effect of ranitidine on the reaction between sodium azide and iodine in an aqueous solution. The calibration graph was linear from 4–24 μg/mL. The drug was determined by measuring the decrease in the absorbance of iodine at 348 nm using a fixed time method. The decrease in the absorbance after 1 minute from the initiation of the reaction was related to the concentration of drug. The detection limit of the procedure was 0.76 μg/mL. The proposed procedure was successfully utilized in the determination of the drug in pharmaceutical preparations with mean recovery in the range of 99.83 ‒ 101.16%.The second method is a colorimetric method, which depends on the measurement of absorbances of tris (o‐phenanthroline) iron(II) [method 2A] and tris (bipyridyl) iron(II) [method 2B] complexes at 512 nm. The complexes obeyed Beer's law over the concentration range of 2–16 μg/mL and 4–40 μg/mL for methods 2A and 2B, respectively. The developed method has been successfully applied for the determination of ranitidine in bulk drugs and pharmaceutical formulations. The common excipients and additives did not interfere in its determination.

Reliable method for the determination of ranitidine by liquid chromatography using a microvolume of plasma

The aim of the present study was to develop a simple method to measure ranitidine, using 100 μl of plasma, by high-performance liquid chromatography with a Symmetry C 18 column and UV detection at 313 nm. Linearity was assessed in the range from 50 to 1500 ng ml −1 and had a correlation coefficient of 0.999. The inter- and intra-day coefficients of variation were less than 7%. The limits of detection and quantitation were 5 and 15 ng ml −1, respectively. Drug levels were determined satisfactorily in three patients. A simple and reliable method was developed which uses a microvolume of plasma, particularly useful in low-weight children.

Development of an HPLC method for the determination of ranitidine and cimetidine in human plasma following SPE

A selective, sensitive and accurate high-performance liquid chromatographic method has been developed, validated and applied for the determination of ranitidine and cimetidine in plasma samples. The effects of mobile phase composition, buffer concentration, mobile phase pH and concentration of organic modifiers on retention of investigated drugs were investigated. Sample preparation was carried out by adding an internal standard, famotidine, and the clean-up procedure was accomplished using solid-phase extraction (SPE). This method uses ultraviolet detection, the separation used a Lichrocart Lichrospher 60 RP-select B column and the mobile phase consisted of 0.2% triethylamine (TEA), 0.04 mol l −1 KH 2PO 4 at pH 6.8 and 14% acetonitrile. The recovery, selectivity, linearity, precision and accuracy of the method were evaluated from spiked human plasma. The method has been implemented to monitor ranitidine levels in clinical samples.

Determination of ranitidine in drugs using a mercury coated platinum ultramicroelectrode and hanging mercury dropping electrode

The voltammetric behavior of ranitidine has been studied in aqueous media with a mercury coated platinum ultramicroelectrode (Hg-UME) and by HMDE. The LSV curves for the electroreduction of ranitidine showed that the compound presents two reduction waves in pH < 4.0 and only one in pH > 4.0, the observed waves being attributed to the reduction of the nitro group to hydroxylamine. A linear relation between the current peak or limiting current and the ranitidine concentration using HMDE or Hg-UME was observed, demonstrating that these ultramicroelectrodes can be used in the analytical determination of ranitidine. An alternative and more sensitive methodology for the analytical determination of ranitidine by SWV was also developed, with a detection limit of 3.5 x 10-8 mol L-1 (or 11 mg L-1). The apparent recovery (AR) studies proved the accuracy and precision of the assay developed. The excipients found in comercial Antak tablets (Glaxo Wellcome) and the generic from EMSâ do not interfere in the determination.

Kinetic Spectrophotometric Method for the Determination of Ranitidine and Nizatidine in Pharmaceuticals

An accurate and simple kinetic method is described for the determination of ranitidine and nizatidine in pure form and in pharmaceuticals. The method is based on the reaction of the compounds with 7-chloro-4-nitrobenz-2-oxa-1,3-diazole in pH 7.4 borate buffer at 60 degrees C for a fixed time of 25 min for both compounds. The absorbance of the reaction product is measured at 495 nm for ranitidine and nizatidine. Calibration graphs were linear over the concentration range of 2-20 microg/mL, with limits of detection of 0.13 (3.7 x 10(-7) M) and 0.25 microg/mL (7.5 x 10(-7) M) for ranitidine and nizatidine, respectively. The proposed method was applied successfully to the determination of ranitidine in tablets and ampoules with average recoveries of 100.26+/-0.69 and 100.29+/-0.59%, respectively, and to the determination of nizatidine in capsules with an average recovery of 104.26+/-0.44%. The results obtained are in good agreement with those obtained by the other methods used for comparison. A proposal of the reaction pathway is also presented.

Direct determination of ranitidine and famotidine by CE in serum, urine and pharmaceutical formulations

A simple and sensitive capillary electrophoresis method using UV detection has been developed for the direct determination of ranitidine (RANT) and famotidine (FAMT) in serum, urine and pharmaceutical formulations. A buffer consisting of 60 mM phosphate buffer adjusted to pH 6.5 was found to provide a very efficient and stable electrophoretic system for the analysis of both drugs. The detection limits obtained were 0.088 μg ml −1 for RANT and 0.16 μg ml −1 for FAMT.

Flow-injection extraction-spectrophotometric method for the determination of ranitidine in pharmaceutical preparations.

The spectrophotometric determination of trace amounts of ranitidine was carried out by liquid-liquid extraction using bromothymol blue with a flow system. The determination of ranitidine in the range of 1 x 10(-5) - 1 x 10(-4) mol l(-1) was possible with a sampling frequency of 40 samples h(-1). The method was satisfactorily applied to the determination of ranitidine in pharmaceutical preparations and the recovery was quantitative and no interferences from excipients were observed.

Rapid determination of ranitidine in human plasma by high-performance liquid chromatography without solvent extraction

A simple high-performance liquid chromatographic procedure was developed for the determination of ranitidine in human plasma. The method entailed direct injection of the plasma samples after deproteination using perchloric acid. The chromatographic separation was accomplished with an isocratic elution using mobile phase consisting of 21 m M disodium hydrogen phosphate–triethylamine-acetonitrile (1000:60:150, v/v), pH 3.5. Analyses were run at a flow-rate of 1.3 ml/min using a μbondapak C 18 column and ultraviolet detection at a wavelength of 320 nm. The method was specific and sensitive, with a quantification limit of approximately 20 ng/ml and a detection limit of 5 ng/ml at a signal-to-noise ratio of 3:1. The mean absolute recovery was about 96%, while the within- and between-day coefficient of variation and percent error values of the assay method were all less than 8%. The linearity was assessed in the range of 20–1000 ng/ml plasma, with a correlation coefficient of greater than 0.999. This method has been used to analyze several hundred human plasma samples for bioavailability studies.

Automated in-tube solid-phase microextraction–liquid chromatography–electrospray ionization mass spectrometry for the determination of ranitidine

The technique of automated in-tube solid-phase microextraction (SPME) coupled with liquid chromatography–electrospray ionization mass spectrometry (LC–ESI-MS) was evaluated for the determination of ranitidine. In-tube SPME is an extraction technique for organic compounds in aqueous samples, in which analytes are extracted from the sample directly into an open tubular capillary column by repeated aspirate/dispense steps. In order to optimize the extraction of ranitidine, several in-tube SPME parameters such as capillary column stationary phase, extraction pH and number and volume of aspirate/dispense steps were investigated. The optimum extraction conditions for ranitidine from aqueous samples were 10 aspirate/dispense steps of 30 μl of sample in 25 m M Tris–HCl (pH 8.5) with an Omegawax 250 capillary column (60 cm×0.25 mm I.D., 0.25 μm film thickness). The ranitidine extracted on the capillary column was easily desorbed with methanol, and then transported to the Supelcosil LC-CN column with the mobile phase methanol–2-propanol–5 M ammonium acetate (50:50:1). The ranitidine eluted from the column was determined by ESI-MS in selected ion monitoring mode. In-tube SPME followed by LC–ESI-MS was performed automatically using the HP 1100 autosampler. Each analysis required 16 min, and carryover of ranitidine in this system was below 1%. The calibration curve of ranitidine in the range of 5–1000 ng/ml was linear with a correlation coefficient of 0.9997 ( n=24), and a detection limit at a signal-to-noise ratio of three was ca. 1.4 ng/ml. The within-day and between-day variations in ranitidine analysis were 2.5 and 6.2% ( n=5), respectively. This method was also applied for the analyses of tablet and urine samples.

Determination of Ranitidine and Salbutamol by Flow Injection Analysis with Chemiluminescence Detection

Flow injection analysis methodology is reported for the determination of ranitidine and salbutamol (in pharmaceutical formulations) based on their chemiluminescent reactions with tris(2,2′-bipyridyl)ruthenium(III) and acidic potassium permanganate, respectively. While the log–log calibration function for ranitidine showed significant non linearity, the precision (measured as relative standard deviation) was 1.7% ( n = 6 1 × 10 −5 M) and the detection limit (3 σ blank) was 6 × 10 −7 M. A linear log–log calibration function was obtained for salbutamol, the precision being 2.7% ( n = 6; 1 × 10 −7 M) with a detection limit (signal to noise ratio = 3) of 2.5 × 10 −8 M.

Simple high-performance liquid chromatographic method for the determination of ranitidine in human plasma

A simple high-performance liquid chromatographic method was developed for the determination of ranitidine in human plasma. Prior to analysis, ranitidine and the internal standard (metoprolol) were extracted from alkalinized plasma samples using dichloromethane. The mobile phase was 0.05 M potassium dihydrogenphosphate–acetonitrile (88:12, v/v) adjusted to pH 6.5. Analysis was run at a flow-rate of 1.3 ml/min and at a detection wavelength of 229 nm. The method is sensitive with a detection limit of 1 ng/ml at a signal-to-noise ratio of 3:1, while the quantification limit was set at 15 ng/ml. The calibration curve was linear over a concentration range of 15–2000 ng/ml. Mean recovery value of the extraction procedure was about 90%, while the within-day and between-day coefficients of variation and percent error values of the assay method were all less than 15%.

Rapid determination of ranitidine in human plasma by high-performance liquid chromatography

An HPLC method has been developed for the quantification of rantidine in plasma for pharmacokinetic studies. Metoclopramide was used as internal standard. The method uses a simple and rapid sample clean-up procedure involving single-step extraction with organic solvent to extract ranitidine from plasma. After evaporation and reconstitution the samples are chromatographed on a 250 mm×4 mm base-stable reversed-phase column with 0.05 M ammonium acetate-acetonitrile, 75∶25 (v/v) as mobile phase and UV detection at 313 nm. The calibration graph was linear for quantities of ranitidine between 10 and 2000 ng mL−1. Intra- and inter-dayCV did not exceed 11.64%. The quantitation limit was 10 ng mL−1 for human plasma. The applicability of this method for pharmacokinetic studies of ranitidine after oral administration are described. Approximately 90 samples can be processed in 24 h.

Optimisation, validation and application of a capillary electrophoresis method for the determination of ranitidine hydrochloride and related substances

Ranitidine hydrochloride is an H 2-antagonist which is widely prescribed for the treatment of peptic ulcers. The drug is marketed in a variety of dosage forms including tablets, syrups and injection solutions. A range of synthetic and degradative impurities of ranitidine are known and currently, these impurities are routinely determined using thin-layer chromatography (TLC). Alternatively a high-performance liquid chromatography (HPLC) method has also been employed in the assay of the pharmaceutical preparation. Unlike TLC, capillary electrophoresis (CE) offers the capability to quantify simultaneously both the active drug content and the levels of the related substances. The advantages of simplicity, selectivity, versatility and ease of use of CE offers a complementary separation technique to the established methods of HPLC and TLC in the determination of ranitidine and its related substances. This work represents a comprehensive evaluation of the performance of a developed CE method in the determination of drug-related impurities in both drug substance and various pharmaceutical formulations. The data obtained clearly shows that the performance of an optimised CE method can be equivalent in terms of sensitivity and precision to that of a HPLC method employed for a similar purpose and offers better selectivity against TLC and HPLC.

Simple and robust high-performance liquid chromatographic method for the determination of ranitidine in microvolumes of human serum.

A simple robust high-performance liquid chromatographic method is described for the determination of ranitidine in microvolumes of human serum. The drug of interest was isolated using liquid-liquid extraction with dichloromethane and back-extraction with 0.1% phosphoric acid and separation was obtained using a reversed-phase column under isocratic conditions, with ultraviolet detection at 313 nm. Intra-day and inter-day coefficients of variation ranged from 1 to 6% and 3 to 10%, respectively. Accuracy of the assay was less than 10% at all concentrations. The limit of detection and the limit of quantitation were 2 and 7 ng/ml, respectively. The linearity was assessed in the range 10-1000 ng/ml. It was shown that a group of common drugs co-administered with ranitidine did not interfere with its determination. The applicability of this method for the pharmacokinetic study of ranitidine following i.v. infusion in patients was demonstrated using only 100 microl of serum. The ruggedness of the assay was demonstrated over a three-year period.

Solid-phase extraction and determination of ranitidine in human plasma by a high-performance liquid chromatographic method utilizing midbore chromatography.

An improved high-performance liquid chromatographic (HPLC) method utilizing solid-phase extraction (SPE) and midbore chromatography was developed for the determination of ranitidine in human plasma. A mobile phase of 20 mM K2HPO4-acetonitrile-triethylamine (87.9:12.0:0.1, v/v) pH 6.0 was used with a phenyl analytical column and ultraviolet detection (UV). The method demonstrated linearity from 25 to 1000 ng/ml in 500 microliters of plasma with a detection limit of 10 ng/ml. The method was utilized in a pharmacokinetic study evaluating the effects of pancreatico-biliary secretions on ranitidine absorption.

Determination of ranitidine in pharmaceutical preparations using manual and flow injection potentiometry and spectrophotometry

New, simple and convenient potentiometric and spectrophotometric methods are described for the determination of ranitidine. The potentiometric technique is based on direct measurements of the drug cation with novel PVC matrix membrane sensors incorporating ranitidine-reineckate, tungstophosphate and tungstosilicate ion association complexes as electroactive compounds with 2-nitrophenyl phenyl ether as plasticizing solvent mediator. These sensors exhibit rapid near-Nernstian stable responses for 10 −2 − 10 −6 M ranitidine over the pH range 4–8, and are used in a flow-through sandwich cell for flow injection determination of the drug. The spectrophotometric method involves the formation of a yellow di(N-nitroso)ranitidine chromophore by reaction of ranitidine with excess nitrite in acetate buffer of pH 4.8 and in the presence of Cu 2+ Br − or micelles as catalyst. Beer's law is obeyed at 450 nm over the range 0.3–12 mg ml −1. Determination of ranitidine in a variety of pharmaceutical dosage forms using the proposed potentiometric and spectrophotometric methods shows an average recovery of 98.4% of the nominal values and a mean standard deviation of 0.5%. No interferences are caused by various drug excipients and diluents. The results compare favourably with those obtained by the liquid Chromatographic method of the US Pharmacopoeia.

Sensitive high-performance thin-layer chromatography method for detection and determination of ranitidine in plasma samples

A high-performance thin-layer chromatographic procedure has been developed for the determination of ranitidine, a H 2-receptor antagonist, in plasma. The detection and quantification were performed without using internal standards. A single-stage extraction procedure was followed for extracting ranitidine from plasma, and a known amount of the extract was spotted on precoated silica gel F254 plates. Ranitidine was quantified using a Shimadzu CS930 dual-wavelength TLC scanner. The method provides a direct estimate of total ranitidine present in the plasma.

Flow injection–fluorimetric method for the determination of ranitidine in pharmaceutical preparations using o-phthalaldehyde

A flow injection–fluorimetric procedure for the determination of ranitidine is proposed. The assay is based on the reaction of the drug with sodium hypochlorite, to produce a primary amine, which reacts with o-phthalaldehyde and 2-mercaptoethanol to form highly fluorescent derivatives. The calibration graph, based on peak area, is linear in the range 20–500 ng ml–1 of ranitidine with an accuracy of 3.4%. The corresponding detection limit is 13 ng ml–1(3.7 pmol). The method was applied to the determination of ranitidine in pharmaceuticals. The recovery was quantitative and no interferences from excipients were observed.