Stress Degradation Behavior of Desipramine Hydrochloride and Development of Suitable Stability-Indicating LC Method

A simple reverse phase liquid chromatographic method was developed for the quantitative determination of desipramine hydrochloride and its related impurities in bulk drugs which is also stability-indicating. During the forced degradation at hydrolysis, oxidative, photolytic and thermal stressed conditions, the degradation results were only observed in the oxidative stress condition. The blend of the degradation product and potential impurities were used to optimize the method by an YMC Pack Pro C₁₈ stationary phase. The LC method employs a linear gradient elution with the water–acetonitrile–trifluoroacetic acid as mobile phase. The flow rate was 1.0 mL min⁻¹ and the detection wavelength 215 nm. The stressed samples were quantified against a qualified reference standard and the mass balance was found close to 99.0% (w/w) when the response of the degradant was considered to be equal to the analyte (i.e. desipramine). The developed RP-LC method was validated in agreement with ICH requirements.

     

Stress Degradation Behavior of Entacapone and Development of LC Stability-Indicating Related Substances and Assay Method

A new, sensitive, stability indicating gradient RP-LC related substances and assay method has been developed for the quantitative determination of entacapone in bulk drugs. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination of buffer and acetonitrile. Buffer consisted of 0.1% orthophosphoric acid, delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 220 nm with a flow rate of 1.5 mL min^?1. In the developed LC method the resolution (R _s ) between entacapone and its three potential process impurities were found to be >2.0. Regression analysis showed an r ² value (correlation coefficient) >0.99 for entacapone and its three potential impurities. This method was capable to detect all three process impurities of entacapone at a level of 0.003% with respect to test concentration of 0.5 mg mL^?1 for a 20 μL injection volume. The inter- and intra-day precision values for all three impurities and for entacapone was found to be within 2.0% RSD. The method has shown good and consistent recoveries for entacapone in bulk drugs (99.2–101.5%) and its three impurities (99.5–102.2%). The test solution was found to be stable in diluent for 48 h. The drug substances were subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in acid stress, base stress and oxidative conditions. The stressed test solutions were assayed against the qualified working standard of entacapone and the mass balance in each case was close to 99.7% indicating that the developed method was stability-indicating. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.     

Stress Degradation Behavior of Entacapone and Development of LC Stability-Indicating Related Substances and Assay Method

A new, sensitive, stability indicating gradient RP-LC related substances and assay method has been developed for the quantitative determination of entacapone in bulk drugs. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination of buffer and acetonitrile. Buffer consisted of 0.1% orthophosphoric acid, delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 220 nm with a flow rate of 1.5 mL min⁻¹. In the developed LC method the resolution (R _s ) between entacapone and its three potential process impurities were found to be >2.0. Regression analysis showed an r ² value (correlation coefficient) >0.99 for entacapone and its three potential impurities. This method was capable to detect all three process impurities of entacapone at a level of 0.003% with respect to test concentration of 0.5 mg mL⁻¹ for a 20 μL injection volume. The inter- and intra-day precision values for all three impurities and for entacapone was found to be within 2.0% RSD. The method has shown good and consistent recoveries for entacapone in bulk drugs (99.2–101.5%) and its three impurities (99.5–102.2%). The test solution was found to be stable in diluent for 48 h. The drug substances were subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in acid stress, base stress and oxidative conditions. The stressed test solutions were assayed against the qualified working standard of entacapone and the mass balance in each case was close to 99.7% indicating that the developed method was stability-indicating. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.

     

Stability-Indicating LC Method for Analysis of Lornoxicam in the Dosage Form

A simple, rapid, and precise method has been developed for quantitative analysis of lornoxicam (Lxm) in pharmaceutical dosage forms. Chromatographic separation of Lxm and its degradation products was achieved on a C₁₈ analytical column with 0.05% (v/v) aqueous trifluoroacetic acid–acetonitrile, 70:30 (v/v), as mobile phase. The flow rate was 1.0 mL min^?1, the column temperature 30 °C, and detection was by absorption at 295 nm using a photodiode-array detector. The number of theoretical plates and tailing factor for Lxm were 6,577 and 1.03, respectively. Lxm was exposed to thermal, photolytic, hydrolytic, and oxidative stress, and the stressed samples were analysed by use of the proposed method. Peak homogeneity data for Lxm in the chromatograms from the stressed samples, obtained by use of the photodiode-array detector, demonstrated the specificity of the method for analysis of Lxm in the presence of the degradation products. The linearity of the method was excellent over the range 10–200 μg mL^?1 Lxm. The correlation coefficient was 0.9999. Relative standard deviations of peak areas from six measurements were always less than 2%. The proposed method was found to be suitable and accurate for quantitative analysis of Lxm and study of its stability.     

Development and Validation of a New Analytical Method for the Determination of Related Components in Tolterodine Tartarate Using LC

A novel liquid chromatographic method has been developed, and validated for the determination of tolterodine tartarate, for its potential three impurities in drug substances and drug products. Efficient chromatographic separation was achieved on a C8 stationary phase (150 × 4.6 mm, 3.5 μm particles) with a simple mobile phase combination delivered in an isocratic mode at a flow rate of 0.8 mL min^?1 and quantitation was carried out using ultraviolet detection. Microwave assisted degradation procedure was employed for stress testing studies in addition to the conventional way of a refluxing method. The results of both studies were compared. In the developed LC method, the resolution between tolterodine and its three potential impurities was found to be greater than 2.0. Regression analysis shows an r value (correlation coefficient) greater than 0.999 for tolterodine and for its three impurities. This method was capable to detect all three impurities of tolterodine at a level below 0.0038% with respect to a test concentration of 0.5 mg mL^?1 for a 10 μL injection volume. The inter- and intra-day precisions for all three impurities and for tolterodine were found to be within 1.1% RSD at its specification level. The method has shown good, consistent recoveries for tolterodine (98.9–101.6%) and for its three impurities (94.5–103.0%). The test solution was found to be stable in the diluent for 48 h. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation, as prescribed by ICH. Degradation was found to occur in alkaline stress condition, while the drug was stable to water hydrolysis, acid hydrolysis, oxidative stress, photolytic and thermal stress. The assay of stressed samples was calculated against a qualified reference standard and the mass balance was found close to 99.5%. Microwave degradations were very fast and comparable to the conventional way of the refluxing method. Robustness studies were carried out and suggested that system suitability parameters were unaffected by small changes in critical factors. The validated method was successfully applied for the determination of tolterodine tartarate in drug substances and drug products.     

Stability-Indicating RP-HPLC Method for Simultaneous Determination of Metformin Hydrochloride and Sitagliptin Phosphate in Dosage Forms

A new stability-indicating high-performance liquid chromatographic method has been developed for simultaneous analysis of metformin hydrochloride (MET) and sitagliptin phosphate (SIT) in pharmaceutical dosage forms. Chromatographic separation was achieved on a C₈ column. The mobile phase was methanol–water 45:55 % (v/v) containing 0.2 % (w/v) n-heptanesulfonic acid and 0.2 % (v/v) triethylamine; the pH was adjusted to 3.0 with orthophosphoric acid. The flow rate was 1 mL min^?1 and the photodiode-array detection wavelength was 267 nm. The linear regression coefficients for metformin and sitagliptin were 0.9998 and 0.9996 in the concentration ranges 50–450, and 10–150 μg mL^?1, respectively. The relative standard deviations for intra and inter-day precision were below 1.5 %. The drugs were subjected to a variety of stress conditions—acidic and basic hydrolysis, and oxidative, photolytic, neutral, and thermal degradation. The products obtained from photolytic degradation were similar to those from neutral hydrolytic degradation and different from produced by acidic and basic hydrolysis. The method resulted in detection of 15 degradation products (D1–D15); among these, the structures of D1, D3, D9, and D13 were identified. The respective mass balance for MET and SIT was found to be close to 97.60 and 99.12 %. The specificity of the method is suitable for a stability-indicating assay.     

A Stability Indicating LC Method for Deferasirox in Bulk Drugs and Pharmaceutical Dosage Forms

A novel, sensitive, stability indicating RP-LC method has been developed for the quantitative determination of deferasirox, its related impurities in both bulk drugs and pharmaceutical dosage forms. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination delivered in an isocratic mode and quantitation was by ultraviolet detection at 245 nm. The mobile phase consisted of buffer, acetonitrile and methanol (50:45:5, v/v) delivered at a flow rate of 1.0 mL min^?1. Buffer consisted of 10 mM potassium dihydrogen orthophosphate monohydrate, pH adjusted to 3.0 by using orthophosphoric acid. In the developed LC method the resolution (R _s ) between deferasirox and its four potential impurities was found to be greater than 2.0. Regression analysis showed an r value (correlation coefficient) greater than 0.999 for deferasirox and its four impurities. This method was capable to detect all four impurities of deferasirox at a level of 0.002% with respect to test concentration of 0.5 mg mL^?1 for a 10 μL injection volume. The inter- and intra-day precision values for all four impurities and for deferasirox was found to be within 2.0% RSD. The method showed good and consistent recoveries for deferasirox in bulk drugs (98.3–101.1%), pharmaceutical dosage forms (100.2–103.1%) and for its all the four impurities (99.7–102.1%). The test solution was found to be stable in methanol for 48 h. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in acid stress hydrolysis. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.95%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.     

Development and Validation of a New LC Method for Analysis of Brimonidine Tartrate and Related Compounds

A novel liquid chromatographic method for analysis three potential impurities in brimonidine tartrate drug substance has been developed and validated. Efficient chromatographic separation was achieved on a C₈ column (250 mm × 4.6 mm, 5-μm particles) with a simple mobile-phase gradient at a flow rate of 1.0 mL min^?1. Quantification was achieved by use of ultraviolet detection at 248 nm. Resolution between brimonidine tartrate and its three potential impurities was greater than 3.0. Regression analysis showed the r value (correlation coefficient) was >0.999 for brimonidine and its three impurities. The method was capable of detecting all three impurities of brimonidine tartrate at levels below 0.07 μg in a test concentration of brimonidine tartrate of 1.0 mg mL^?1 and for an injection volume of 10 μL. A solution of brimonidine tartrate in acetonitrile–water 2:8 (v/v) was stable for 48 h. The drug was subjected to stress conditions as prescribed by the ICH. Degradation was found to occur slightly under oxidative stress conditions but the drug was stable to aqueous, acidic, and basic hydrolysis, and photolytic and thermal stress. The assay of the stressed samples was calculated relative to a qualified reference standard and the mass balance was found close to 99.8%. The method was validated for linearity, accuracy, precision, and robustness.     

A Stability-Indicating LC Method for Analysis of Balsalazide Disodium in the Bulk Drug and in Pharmaceutical Dosage Forms

A novel, sensitive, stability-indicating gradient RP-LC method has been developed for quantitative analysis of balsalazide disodium and its related impurities both in the bulk drug and in pharmaceutical dosage forms. Efficient chromatographic separation was achieved on a C₁₈ stationary phase with a simple mobile-phase gradient prepared from methanol and phosphate buffer (10 mm potassium dihydrogen orthophosphate monohydrate, adjusted to pH 2.5 by addition of orthophosphoric acid). The mobile-phase flow rate was 1.0 mL min^?1. Quantification was achieved by use of ultraviolet detection at 240 nm. Under these conditions resolution of balsalazide disodium from its three potential impurities was greater than 2.0. Regression analysis resulted in a correlation coefficient greater than 0.99 for balsalazide disodium and all three impurities. This method was capable of detecting the three impurities at 0.003% of the test concentration of 0.3 mg mL^?1, using an injection volume of 10 μL. Inter-day and intra-day precision for all three impurities and for balsalazide disodium was within 2.0% RSD. Recovery of balsalazide disodium from the bulk drug (99.2–101.5%) and from pharmaceutical dosage forms (99.8–101.3%), and recovery of the three impurities (99.1–102.1%) was consistently good. The test solution was found to be stable in 70:30 (v/v) methanol–water for 48 h. When the drug was subjected to hydrolytic, oxidative, photolytic, and thermal stress, acidic and alkaline hydrolysis and oxidizing conditions led to substantial degradation. The RP-LC method was validated for linearity, accuracy, precision, and robustness.     

Determination of Dutasteride by LC: Validation and Application of the Method

A simple, rapid, and stability-indicating reversed-phase high-performance liquid chromatographic (LC) method for analysis for dutasteride has been successfully developed. Chromatography was performed on a 150 mm × 4.6 mm C₁₈ column with acetonitrile–water 60:40 (v/v) as isocratic mobile phase at 1.0 mL min^?1. Ultraviolet detection of dutasteride was at 210 nm. Its retention time was approximately 10 min and its peak was symmetrical. Response was a linear function of concentration over the range 0.2–1 μg mL^?1 (R ² = 0.997) and the limits of detection and quantitation were was 0.05 and 0.10 μg mL^?1, respectively. The method was validated for linearity, precision, repeatability, sensitivity, and selectivity. Selectivity was validated by subjecting dutasteride stock solution to photolytic, acidic, basic, oxidative, and thermal degradation. The peaks from the degradation products did not interfere with that from dutasteride. The method was used to quantify dutasteride in pharmaceutical preparations.     

Stress Degradation Studies on Aripiprazole and Development of a Validated Stability Indicating LC Method

The present paper describes the development of a stability indicating reversed phase column liquid chromatographic method for aripiprazole in the presence of its impurities and degradation products generated from forced decomposition studies. The drug substance was subjected to stress conditions of aqueous hydrolysis, oxidative, photolytic and thermal stress degradation. The degradation of aripiprazole was observed under acid hydrolysis and peroxide. The drug was found to be stable to other stress conditions attempted. Successful separation of the drug from the synthetic impurities and degradation products formed under stress conditions was achieved on an Inertsil phenyl column using a mixture of 0.2% trifluoroacetic acid and acetonitrile (55:45, v/v). The developed LC method was validated with respect to linearity, accuracy, precision, specificity and robustness. The assay method was found linear in the range of 25–200 μg mL^?1 with a correlation coefficient of 0.9999 and the linearity of the impurities were established from LOQ to 0.3%. Recoveries of the assay and impurities were found between 97.2 and 104.6%. The developed LC method for the related substances and assay determination of aripiprazole can be used to evaluate the quality of regular production samples. It can also be used to test the stability samples of aripiprazole. To the best of our knowledge, the validated stability indicating LC method which separates all the impurities disclosed in this investigation was not published elsewhere.     

Forced Degradation Study to Develop and Validate Stability-Indicating RP-LC for Quantification of Ropinirole Hydrochloride in Its Modified Release Tablets

A forced degradation study on ropinirole hydrochloride in bulk and in its modified release tablets was conducted under the conditions of hydrolysis, oxidation and photolysis in order to develop an isocratic stability-indicating LC-UV method for quantification of the drug in tablets. An impurity peak in standard solution was found to increase under acidic and neutral hydrolytic conditions while another degradation product was formed under alkaline condition. The drug and its degradation products were optimally resolved on a Hypersil C₁₈ column with mobile phase composed of diammonium hydrogen orthophosphate (0.05 M; pH 7.2), tetrahydrofuran and methanol (80:15:5% v/v) at a flow rate of 1.0 mL min^?1 at 30 °C using 250 nm as detection wavelength. The method was linear in the range of 0.05–50 μg mL^?1 drug concentrations. The %RSD of inter- and intra-day precision studies was <1. The system suitability parameters remained unaffected during quantification of the drug on three different LC systems. Excellent recoveries (101.59–102.28%) proved that the method was sufficiently accurate. The LOD and LOQ were found to be 0.012 and 0.040 μg mL^?1, respectively. Degradation behaviour of the drug in both bulk and tablets was similar. The drug was very unstable to hydrolytic conditions but stable to oxidative and photolytic conditions. The method can be used for rapid and accurate quantification of ropinirole hydrochloride in tablets during stability testing. Based on chemical reactivity of ropinirole in different media, the degradation products were suspected to be different from the known impurities of the drug.     

Development and Validation of a New LC Method for Analysis of Brimonidine Tartrate and Related Compounds

A novel liquid chromatographic method for analysis three potential impurities in brimonidine tartrate drug substance has been developed and validated. Efficient chromatographic separation was achieved on a C₈ column (250 mm × 4.6 mm, 5-μm particles) with a simple mobile-phase gradient at a flow rate of 1.0 mL min⁻¹. Quantification was achieved by use of ultraviolet detection at 248 nm. Resolution between brimonidine tartrate and its three potential impurities was greater than 3.0. Regression analysis showed the r value (correlation coefficient) was >0.999 for brimonidine and its three impurities. The method was capable of detecting all three impurities of brimonidine tartrate at levels below 0.07 μg in a test concentration of brimonidine tartrate of 1.0 mg mL⁻¹ and for an injection volume of 10 μL. A solution of brimonidine tartrate in acetonitrile–water 2:8 (v/v) was stable for 48 h. The drug was subjected to stress conditions as prescribed by the ICH. Degradation was found to occur slightly under oxidative stress conditions but the drug was stable to aqueous, acidic, and basic hydrolysis, and photolytic and thermal stress. The assay of the stressed samples was calculated relative to a qualified reference standard and the mass balance was found close to 99.8%. The method was validated for linearity, accuracy, precision, and robustness.

     

A Validated LC Method for Determination of Trace Impurities in Technical Triadimefon

A simple and sensitive liquid chromatography with ultraviolet detection (LC?CUV) method was developed for the determination of three impurities with a content over 0.1% (w/w) in technical triadimefon. A Gemini C₁₈ column (5 ??m, 250 mm × 4.6 mm i.d.) was used for the chromatographic separations. The samples were separated by gradient elution with water (solvent A) and methanol (solvent B) using the following conditions: 70% A isocratic for 12 min, linear to 0% A within 8 min, and isocratic for 10 min at 0% A with a flow rate of 1.0 mL min^?1. Chromatograms were recorded at an absorption wavelength of 280 nm. The chromatographic resolutions between triadimefon and its potential impurities A, B, and C were greater than 3. The developed LC method was validated with respect to linearity, accuracy, precision, and robustness. This method was successfully applied to analyze the impurities in commercial technical triadimefon. In addition, the structures of the three impurities were identified to be (A) 4-chlorophenol, (B) 1-(2,4-dichlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)-2-butanone, and (C) 1,1-bis(4-chlorophenoxy)-3,3-dimethyl-2-butanone.     

Development and Validation of a New Analytical Method for the Determination of Related Components in Quetiapine Hemifumarate

A simple, sensitive isocratic rapid resolution liquid chromatographic assay method has been developed for the quantitative determination of quetiapine hemifumarate in bulk active pharmaceutical ingredient, used for the treatment of schizophrenia. The developed method is also applicable for the process related impurities determination. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination delivered in a isocratic mode and quantification was by ultraviolet detection at 225 nm at a flow rate of 1.0 mL min^?1. In the developed LC method the resolution between quetiapine hemifumarate and its three potential impurities was found to be greater than 2.0. Regression analysis showed an r value (correlation coefficient) greater than 0.99 for quetiapine hemifumarate and its three impurities. This method was capable to detect all three impurities of quetiapine hemifumarate at a level of 0.003% with respect to test concentration of 1.0 mg mL^?1 for a 3 μL injection volume. The bulk active pharmaceutical ingredient was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in oxidative stress conditions. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.5%. The developed RR-LC method was validated with respect to linearity, accuracy, precision and robustness.     

Stress Degradation Studies of Anagliptin,Development of Validated Stability Indicating Method,Degradation Kinetics Study,Identification and Isolation of Degradation Products

A gradient-specific stability indicating HPLC method was developed and validated for the determination of the antidiabetic agent anagliptin in laboratory mixtures. Reversed-phase chromatography was performed using a Shimadzu LC-20 AD pump (binary), Shimadzu PDA M-20A diode array detector, and Waters Symmetry C-18 column (150?×?4.6 mm, 3.5 µm) maintained at a column oven temperature of 40 °C with UV detection at 247 nm. A gradient program was run at flow rate of 1 mL min^?1. Mobile phase A consisted of a mixture of acetate buffer(10 mm) pH 5/methanol/acetonitrile in the ratio of 90:5:5. Mobile phase B consisted of a mixture of acetate buffer (10 mm) pH 5/methanol/acetonitrile in the ratio of 50:25:25. The method was validated according International Conference of Harmonization (ICH) guidelines. Linearity was observed in the concentration range of 10–120 µg/mL with regression coefficient r²(0.999). The LOD was found to be 7.8 µg/mL and LOQ was found to be 22.68 µg/mL. Anagliptin was subjected to stresses such as acidic, alkali, oxidation, photolysis, and thermal conditions. The proposed method was validated as per ICH guidelines and was found to be accurate, precise, and specific. The drug showed significant degradation in alkaline and oxidative conditions. Alkaline and oxidative degradation followed first-order kinetics. Degradation rate constant and half-lives were determined. Degradation products in alkaline and oxidative conditions were identified by LC–MS. One major degradation product was isolated from each condition by preparative HPLC. These degradation products were characterized by ¹H NMR, ¹³C NMR, DEPT, D₂O exchange, MS/MS, HRMS, and IR techniques. From the spectral data the alkaline degradation product was characterized as 1-{2-[1-(2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamido)-methyl-propan-2-yl-amino]acetyl}pyrrolidine-2-carboxamide. The oxidative degradation product was characterized as N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo-[1,5-a]pyrimidine-N-oxido-6-carboxamide.     

Simultaneous Determination of Impurities in Ropinirole Tablets by an Improved HPLC Method Coupled with Diode Array Detection

A gradient HPLC method coupled with diode array detection was developed and fully validated for the analysis of impurities in ropinirole using a Kromasil^® C8 100 Å (250 × 4.6 mm, 5 μm) column with a flow rate 1.0 mL min^?1 and detection at 250 nm. The mobile phase component A consisted of a mixture of 19.6 mM aqueous potassium dihydrogen phosphate–acetonitrile (98:2 v/v), pH adjusted to 7.0 with triethylamine and the mobile phase component B consisted of acetonitrile. The method was validated in terms of linearity, sensitivity, precision, accuracy and stability. The calibration curves for ropinirole and its five impurities showed good linearity (r > 0.998) within the calibration ranges tested. The intra- and inter-day RSD values were <3.9 %, while the relative percentage error E _r was <5.8 % for all compounds. Accelerated stability studies performed under various stress conditions including oxidation, hydrolysis and UV light irradiation at 254 nm proved the selectivity of the procedure. Long-term stability studies performed on blistered tablets and under various conditions of heat and humidity indicate the presence of four of the studied impurities in less than 0.07 %. The method was applied successfully to the detection and determination of ropinirole impurities in pharmaceutical formulations.     

Development and Validation of a New Analytical Method for the Determination of Related Components and Assay of Ranolazine in Bulk Drug and Pharmaceutical Dosage Forms by LC

A novel liquid chromatographic method has been developed and validated for the determination of ranolazine, its potential four impurities in drug substance and drug products. Efficient chromatographic separation was achieved on a C18 stationary phase (150 × 4.6 mm, 3.0 microns particles) with simple mobile phase combination delivered in gradient mode at a flow rate of 1.0 mL min^?1 at 210 nm. In the developed method, the resolution between ranolazine and its four potential impurities was found to be greater than 2.0. Regression analysis shows an r value (correlation coefficient) greater than 0.999 for ranolazine and for its four impurities. This method was capable to detect all four impurities of ranolazine at a level below 0.004% with respect to test concentration of 1.0 mg mL^?1 for a 10 μL injection volume. The method has shown good, consistent recoveries for ranolazine (98.8–101.1%) and for its four impurities (97.2–100.3). The test solution was found to be stable in the diluent for 48 h. The drug was subjected to stress conditions. The mass balance was found close to 99.5%.     

HPLC Separation of Nimesulide and Five Impurities using a Narrow-Bore Monolithic Column: Application to Photo-Degradation Studies

Nimesulide and its fine impurities were separated using the new narrow-bore FastGradient monolithic column (50 × 2.0 mm i.d.). The mobile phase was a mixture of NH₄H₂PO₄ (10 mmol L^?1, pH 7)/ACN (69:31 v/v) and UV detection was carried out at 230 nm. Depending on the flow rate of the mobile phase (0.5?C1.0 mL min^?1), efficient separation of the six compounds could be achieved within 5?C10 min. The developed HPLC method was validated in terms of linearity, limits of detection and quantitation, precision, selectivity, and accuracy. Application to the photo-stability of nimesulide revealed a ca. 50% degradation of the active pharmaceutical ingredient within 24 h. Impurity D was also identified at a maximum level of 0.46% (24 h).