ABSTRACT
This paper deals with development and validation of a high performance liquid chromatographic method for the quantitative determination of disodium EDTA (Ethylenediaminetetraacetic acid) in Meropenem active pharmaceutical ingredient (API). EDTA was derivatized with Ferric chloride solution by heating at 70 °C in water bath for about 20 minutes and the chromatographic separation achieved by injecting 100 µL of the derivatized mixture into a Waters HPLC system with photodiode array detector using a Phenomenex Luna C18(2) column (250 × 4.6 mm), 5 µ. The mobile phase consisting of 5% methanol and 95% of 0.7 g/L solution of Tetra butyl ammonium bromide and 4.6 g/L solution of sodium acetate trihydrate in water (pH adjusted to 4.0 with the help of acetic acid glacial) and a flow rate of 1 milliliter/minute. EDTA eluted at approximately 6 minutes. The method was suitably validated with respect to specificity, linearity of response, precision, accuracy, ruggedness, stability in analytical solution, limit of quantitation and detection and robustness for its intended use.
ABSTRACT
Alkyl methanesulfonates have been highlighted as potential genotoxic impurities (PGIs). A sensitive LC/MS/MS method was developed and validated for the determination of Alkyl methanesulfonate impurities in Emtricitabine API (active pharmaceutical ingredient). LC/MS/MS method on Zorbax SB C(18) column (150 × 4.6 mm i.d.), 3.5 µm, with electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode was used. The proposed method was specific, linear, accurate, rugged and precise. The calibration curves showed good linearity over the concentration range of 0.0025 µg/ml to 0.3 µg/ml the correlation coefficient was >0.999 in each case. Method had very low limit of detection (LOD) and limit of quantification (LOQ) as 0.3 µg/g and 0.4 µg/g respectively for both the analytes. Accuracy was observed within 80%-120% for both the analytes. This method can be further extended a good quality control tool for low level quantitation of Alkyl methanesulfonate impurities in other API.
ABSTRACT
Methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) have been highlighted as potential genotoxic impurities (PGIs). A sensitive LC/MS/MS method is developed and validated for the determination of MMS and EMS impurities in both Lopinavir and Ritonavir Active pharmaceutical ingredient. Method utilizes, Atlantis T3 column with electrospray ionization in multiple reactions monitoring (MRM) mode for quantitation of impurities. The proposed method is specific, linear, accurate and precise. The calibration curves show good linearity over the concentration range of 0.01-0.23 µg/mL for MMS and 0.005-0.23 µg/mL for EMS. The correlation coefficient obtained is >0.99 in each case. Method has very low limit of detection (LOD) and quantification (LOQ). LOD and LOQ of MMS and EMS are as low as â¼0.002 µg/mL and â¼0.01 µg/mL respectively. Method has accuracy within 80-120% for both the analytes. This method is a good quality control tool for quantitation of MMS and EMS impurities at very low levels in Lopinavir and Ritonavir.
Subject(s)
Chromatography, Liquid/methods , Ethyl Methanesulfonate/analysis , HIV Protease Inhibitors/chemistry , Methyl Methanesulfonate/analysis , Pyrimidinones/chemistry , Ritonavir/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Limit of Detection , Lopinavir , Reference Standards , Tandem Mass SpectrometryABSTRACT
This present paper deals with the development and validation of a stability indicating high performance liquid chromatographic method for the quantitative determination of Memantine hydrochloride. Memantine hydrochloride was derivatized with 0.015 M 9-fluorenylmethyl chloroformate (FMOC) and 0.5 M borate buffer solution by keeping it at room temperature for about 20 minutes and the chromatographic separation achieved by injecting 10 muL of the derivatized mixture into a Waters HPLC system with photodiode array detector using a kromasil C18 column (150 x 4.6 mm), 5 mu. The mobile phase consisting of 80% acetonitrile and 20% phosphate buffer solution and a flow rate of 2 milliliter/minute. The Memantine was eluted at approximately 7.5 minutes. The volume of FMOC used in derivatization, concentration of FMOC and derivatization time was optimized and used. Forced degradation studies were performed on bulk sample of Memantine hydrochloride using acid (5.0 Normal (N) hydrochloric acid), base (1.0 N sodium hydroxide), oxidation (30% hydrogen peroxide), thermal (105 degrees C), photolytic and humidity conditions. The developed LC method was validated with respect to specificity, precision (% RSD about 0.70%), linearity (linearity of range about 70-130 mug/mL), ruggedness (Overall % RSD about 0.35%), stability in analytical solution (Cumulative % RSD about 0.11% after 1450 min.) and robustness.
ABSTRACT
Six unsymmetrical diorganyltellurium(IV) dichlorides RR'TeCl2 (where R= phenacyl-, 1-naphthacyl-, and styrylacyl- and R' = p-methoxyphenyl, p-hydroxyphenyl-, and 3-methyl-4-hydoxyphenyl-) were tested for their antibacterial activity against gram-positive (Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 25923) and gram-negative (Escherichia coli ATCC 25922. Pseudomonas aeruginosa ATCC 27853 and Salmonella sp.) bacteria. Antibacterial activity was measured by disk diffusion method. Inhibition zones demonstrated that all the compounds showed good activity against gram-negative strains. Phenacyl (3-methyl-4-hydroxyphenyl) tellurium(IV) dichloride and naphthacyl (3-methyl-4-hydroxyphenyl) tellurium(IV) dichloride showed significant activity against both gram-positive and gram-negative strains. Among the tested compounds, the former exhibited maximum activity against gram-positive bacteria, while the latter against all the bacteria under study and styrylacyl (p-methoxyphenyl) tellurium(IV) dichloride against all the three gram-negative bacteria.
