Search

Simple, accurate, precise and stable indicating HPLC methods were developed and validated to determine both related substances and the assay content of Remogliflozin etabonate (RME). The separation was established under optimized chromatographic condition using Waters e2695 HPLC coupled to Ultraviolet detector (UV) at 228 nm with Inertsil ODS-3V C18 column (250 mm x 4.6 mm, 5 μm), injection volume 10 μl for related substances and 20 μl for assay content determination. The mobile phase consisted of 10 mM KH2PO4 buffer with ortho-phosphoric acid pH 2.5. Gradient elution was maintained at a flow rate of 1.0 ml/min using 45°C column oven temperature for determination of the related substances and isocratic elution was maintained at a flow rate of 1.2 ml/min for assay content. The retention time for RME-01, RME-02, RME-03 and RME-04, RME-05 and RME were about 41.74 min, 11.42 min, 20.38 min, 37.16 min, 49.93 min, 25.05 min respectively. The linearity was found to be in the concentration range of 0.312-2.341 μg/ mL for RME-01, 0.306-2.292 μg/ mL for RME-02, 0.306-2.297 μg/ ml for RME-03 and 0.294-2.203 μg/mL for RME-04. The RME was subjected to acid, base, oxidation, and thermal degradation stress conditions. The method was validated according to the ICH guidelines for specificity, precision, linearity, accuracy and robustness and the values were found to be within the limits. [ABSTRACT FROM AUTHOR]

A novel stability-indicating reversed phase liquid chromatographic (RP-LC) method was developed for the determination of purity of Nizatidine in Nizatidine oral solutions in the presence of its impurities and degradation products. Two unknown impurities were formed in the formulated drug under the stress conditions (40°C/75% RH for 3 months), with relative retention times (RRTs) 0.93 and 2.14. The two degradant impurities were isolated and characterized using liquid chromatography mass spectrometry (LC-MS). Chromatographic method was developed and validated for Nizatidine United States Pharmacopeia (USP) impurities along with the two degradant impurities. Total 13 impurities were well separated and not interfering with placebo peaks in oral solution. The method was developed using C-18 column in gradient elution mode. The eluted compounds were monitored at 254 nm. Nizatidine was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. The degradation products were well resolved from main peak and its impurities, proving the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization guidelines with respect to specificity, limit of detection, limit of quantification, precision, linearity, accuracy, robustness, and ruggedness. [ABSTRACT FROM AUTHOR]

Valganciclovir hydrochloride (1) is used for the treatment of cytomegalovirus (CMV) retinitis in patients with weakened immune systems. Valganciclovir hydrochloride is a hydrochloride salt of L-valyl ester of ganciclovir (2) that exists as a mixture of two diastereomers. According to the U.S. Food and Drug Administration specifications, the diastereomeric ratio of valganciclovir hydrochloride1should be maintained in the range 55:45 to 45:55. According to the U.S. Food and Drug Administration specifications, the diastereomeric ratio of valganciclovir hydrochloride1should be maintained in the range 55:45 to 45:55. During the process development of valganciclovir hydrochloride, six related substances (impurities) were observed along with the final active pharmaceutical ingredient. Among these six impurities, ganciclovir (2) and guanine (3) are the key starting materials and degraded impurities of ganciclovir, respectively. The remaining four impurities were identified as isovalganciclovir hydrochloride (4), methoxymethylguanine (5),O-acetoxy ganciclovir (6), and isovalarylganciclovir (7). The present work describes the synthesis and characterization of these four impurities. [ABSTRACT FROM AUTHOR]

A validated HPLC method was developed for the analysis of paracetamol, psedoephedrine, triprolidine, methylparaben, propylparaben, sodium benzoate, and their related substances including p-aminophenol, triprolidine Z-isomer, 4-hydroxy benzoic acid, and 4-chloracetailide in syrup using symmetry C18 column at 25°C with UV detection at 214 nm. A linear gradient elution was employed starting with 100% mobile phase A and 0% mobile phase B for 5 min to reach 40% mobile phase A and 60% mobile phase B at 16 min then 0% mobile phase A and 100% mobile phase B at 28 min. Total run time is 30 min using solution of 28 mM sodium dihydrogen phosphate containing 2.6 mM hexanesulphonic acid sodium salt and adjusted to apparent pH 3.0 with phosphoric acid–acetonitrile in ratios of (90:10 v/v) and (60:40 v/v) as mobile phase A and mobile phase B, respectively. All mentioned compounds have been successfully separated and quantified using the developed method. The developed method was linear with (r = 0.9999) for all compounds. The proposed method was completely validated. [ABSTRACT FROM AUTHOR]

In the present study, simultaneous quantification of Abacavir, Lamivudine, and Zidovudine related substances in fixed dosed combination tablet is performed using a reversed-phase High-Performance Liquid Chromatography. The three drugs and its related substances were resolved using a mobile phase containing acetate buffer of pH 3.0, methanol, and acetonitrile in ternary gradient elution mode. The separation was achieved by using a C18, 250 × 4.6 mm 5µ HPLC column. The three main active constituents along with eleven related substances were resolved in this method. The novel method was validated to meet the requirements for global regulatory filing. The method was then successfully migrated to Ultra-Performance Liquid Chromatography (UPLC™) to reduce run time and improve sample throughput. The results confirm that the method is stability-indicating, accurate, precise, and robust. Currently, the HPLC method is being used for the on-going stability analysis of manufactured batches. [ABSTRACT FROM AUTHOR]

The advent of UPLC (known more widely as U-HPLC) brought with it the prospect of achieving high efficiencies through the use of sub-2 µm particles but it has been used more to achieve fast separations using short columns. It was therefore sought to assess whether the efficiency obtainable on such short columns was sufficient for a range of pharmaceutical applications involving active pharmaceutical ingredients (APIs) Mobile phase optimization was required, but this could be done very quickly without resorting to computer-aided strategies. It proved possible to separate paroxetine from its related substances in under 1.2 min, to reduce by 1/10th the time needed for a routine QC assay, to rapidly develop conditions employing on-column sample focusing that allowed the separation and detection of low levels of ‘worst-case scenario’ drugs that might be involved in cleaning validation, and, using a longer column, achieve a rapid separation of benzodiazepines suitable for an identity test. While mobile phase optimization could be carried out quickly to produce very fast separations, it was clear from the benzodiazepine example, in particular, that there is still scope in UPLC for employing longer columns and/or stationary phase selectivity other than that offered by C18-silicas. [ABSTRACT FROM AUTHOR]

Vardenafil hydrochloride trihydrate (Levitra) is used to treat erectile dysfunction (ED) and is an inhibitor of phosphodiesterase type 5 (PDE-5) enzyme. It maintains higher levels of cyclic guanosine monophosphate (cGMP), relaxes smooth muscles, promotes penile blood flow, and enhances erectile function. During the bulk drug synthesis of vardenafil hydrochloride trihydrate, six related substances (impurities), vardenafil dimer, vardenafil N-oxide, vardenafil glycene, vardenafil oxopiperazine, vardenafil oxoacetic acid, and phenyl vardenafil were identified, and these are reported herein for the first time. The present work describes the synthesis and characterization of these impurities. [ABSTRACT FROM AUTHOR]

A simple, fast, and sensitive HPLC method with UV detection has been developed for the quantitation of omeprazole (OMZ) and major related substances in raw material and pharmaceutical formulation (paste) using a column of reduced length (50 mm) and diameter (2.1 mm) packed with hybrid particles. Chromatographic conditions were: 25°C, 1 µl injection volume, and UV detection at WV of 280 nm. The flow rate was 0.3 mL/min using methanol-phosphate buffer (pH 7.6) (40:60) as the mobile phase. Chromatographic purity was also determined with the same chromatographic conditions. The method was validated according to international guidelines (ICH guidelines) for specificity, linearity, LOD, LOQ, precision, accuracy, and robustness. The HPLC-UV method was found to be suitable for the quality control and stability studies of OMZ in a pharmaceutical formulation. [ABSTRACT FROM AUTHOR]

Five related substances (impurities) were detected in lacidipine bulk drug substance by a simple high-performance liquid chromatographic method (HPLC) and were identified by liquid chromatography-mass spectrometry (LC-MS). These related substances were independently synthesized, characterized, and co-injected with the sample containing impurities. [ABSTRACT FROM AUTHOR]

A simiple, rapid, and highly sensitive fast microbore HPLC method with UV detection has been developed for the quantitation of coenzyme Q10 (Co-Q10) and related substances in raw material, pharmaceutical, and cosmetic formulations using a column with hybrid particles. Chromatographic conditions were: 30ºC column temperature, 1 µL injection volume at 275 nm. The Co-Q10 analysis was performed within 2.5 minutes with a flow rate of 0.3 mL/min. with a mobile phase consisted of 100% methanol, and the related substances were separated with a gradient elution based on methanol-water. The developed method was validated for selectivity, linearity, precision, accuracy, and robutness. The method was found to be suitable for the quality control of Co-Q10 in pharmaceutical and cosmetic products, as well as the stability indicating studies. [ABSTRACT FROM AUTHOR]