Y.Ravindra Kumar

Impurity profile study of loratadine

Three unknown impurities in loratadine bulk drug at levels below 0.1% (ranging from 0.05 to 0.1%) were detected by a simple isocratic reversed-phase high performance liquid chromatography (HPLC). These impurities were isolated from mother liquor sample of loratadine using reversed-phase preparative HPLC. Based on the spectral data (IR, NMR and MS) the structures of these impurities were characterized as 11-(N-carboethoxy-4-piperidylidene)-6,11-dihydro-5H-benzo(5,6) cyclopenta(1,2-b)-pyridine (I), 8-bromo-11-(N-carboethoxy-4-piperidylidene)-6,11-dihydro-5H-benzo(5,6) cyclopenta (1,2-b)-pyridine (II) and 8-chloro-11-(N-carboethoxy-4-piperidylidene)-5H-benzo(5,6) cyclopenta (1,2-b)-pyridine (III). The synthesis of these impurities was discussed.

Application of LC–MS/MS for the identification of a polar impurity in mosapride, a gastroprokinetic drug

In the impurity profile of mosapride a polar impurity (0.1%) was detected in HPLC with respect to mosapride. Based on the mass spectral data obtained by LC-MS/MS analysis this impurity structure was characterised as 4-amino-5-chloro-2-ethoxy-N-[[(4-benzyl)-2-morphinyl] methyl] benzamide. It is interesting to note that this impurity is potent analogue of mosapride, which will have much higher gastroprokinetic activity than metoclopramide. This impurity was synthesised from an unambiguous route and confirmed the structure by collecting various spectral data and the formation is discussed. To our knowledge this compound was not reported as process impurity elsewhere.

DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING UPLC METHOD, IDENTIFICATION, AND CHARACTERIZATION OF THREE DEGRADANT IMPURITIES IN PHARMACEUTICAL DOSAGE FORM OF RABEPRAZOLE SODIUM

A simple, sensitive, and reproducible ultra performance liquid chromatography (UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of Rabeprazole Sodium and its three potential degradant impurities along with other six impurities in pharmaceutical dosage forms. Three unknown impurities of Rabeprazole, a proton pump inhibitor, were formed in the formulated drug under the stress conditions, [40°C/75% Relative humidity (RH) for 6 months] with relative retention times (RRTs) 0.10, 0.18, and 0.31. A thorough study was undertaken to characterize these potential degradants. These impurities were enriched by using various stressed conditions, isolated using preparative HPLC and characterized by NMR and MS. On the basis of the spectral data, the Impurity-I, II, and III were characterized as 2-Amino-1H-benzimidazole, 1H-Benzimidazol-2-ol, and 2-Benzimidazolethiol. Chromatographic separation was achieved on Acquity UPLC, RP18 column (100 × 2.1 mm i.d., 1.7 µm particle size). The instrument was set at a flow rate of 0.4 mL/min, the column oven temperature was maintained at 25°C, and the eluted compounds were monitored at 280 nm. The resolution between Rabeprazole and its nine impurities was greater than 1.5. Method was validated as per ICH guidelines.

LC–MS/MS and NMR Characterization of Key Impurities in Linagliptin and Pramipexole

A sensitive, rugged, and robust LC-MS/MS and NMR analysis has been developed for the identification and characterization of key impurities of Linagliptin and Pramipexole. Linagliptin is used in the treatment of Type-2 diabetes. Linagliptin is a DPP-4 inhibitor which is an enzyme that degrades the incretin hormones (glucagon like peptide-1(GLP)) and glucose dependent insulinotropic polypeptide (GIP). Both these hormones increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose 20 levels. Pramipexole is a dopamine agonist of the non-ergoline class indicated for the treatment of Parkinson’s disease and restless legs Q1 syndrome. Parkinson’s disease is a neurodegenerative disease that affects the basal ganglia component, i.e., substantial nigra. Observed one of the key impurities in the analytical HPLC at around 1.30RRT in Lingliptin. To further characterize the impurity, the impurity was synthesized in presence of dibromo methane and was subjected to flash chromatography for further isolation. Thus isolated impurity was subjected to NMR and mass analysis for structure identification. Similarly observed another key impurity in Pramipexole at around 0.96RRT. This impurity was enriched in presence of formaldehyde and was subjected to preparative HPLC for isolation and further characterized by LC-MS and NMR.

Structural studies on the impurities of troglitazone

The impurity profile study of troglitazone has been carried out primarily by (liquid chromatography-mass spectrometry) LC-MS. Four process-related impurities have been detected by LC-MS and were confirmed by co-injection with authentic samples. Apart from the process-related impurities, two polar by-products were characterized by mass spectral data and comparison with reference samples, while one non-polar by-product and one degradation product have been isolated by means of preparative HPLC and characterized by 2D NMR and mass spectral study. Single-crystal X-ray diffraction studies have been carried out on the degradation product. The formation and characterization of these by-products and degradation product are discussed.

LC–MS/MS and NMR characterization of forced degradation products of mirabegron

ABSTRACT A rapid, precise, and reliable liquid chromatography tandem mass spectrometry (LC–MS/MS) method has been developed for the characterization of stressed degradation products of mirabegron. It is used in the treatment of overactive bladder and administered to treat urinary symptoms such as urgency or frequency and incontinence. It also works by relaxing the muscles around bladder. Mirabegron was subjected to hydrolysis (acidic, alkaline, and neutral) and peroxidation, as per ICH-specified conditions. The drug showed degradation under stress conditions. However, it was stable to neutral conditions. A total of seven degradation products were observed and the chromatographic separation of the drug and its degradation products was achieved on X-TerraRP-8 (250 mm × 4.6 mm, i.d., 5 µm) column using 0.01 M ammonium acetate as mobile phase-A and 60:40 ratio of acetonitrile (ACN):water as mobile phase-B. The degradation products were characterized by LC–MS/MS and its fragmentation pathways were proposed. Probable possible structures were drawn based on parent and daughter molecular ions. One peroxide degradant impurity was isolated using preparative LC and characterized using liquid chromatography–mass spectrometry and NMR data. GRAPHICAL ABSTRACT

A Validated method for determination of Metabisulfite content in Cetrizine Dihydrochloride and Ambroxol Hydrochloride 5+30mg/5mL syrup by Ion exchange chromatography.

A commercial, particular and strong Ion Chromatography method was developed for the quantitative determination of metabisulfite content in Cetrizine Ambroxol syrup. The method was developed using Ion pac AS11HC Column, 250 X 4.6mm X 5.0 m column with mobile phase containing 18mM sodium hydroxide in water. The eluted compounds were monitored using conductivity detector. The developed method was validated as per ICH guidelines with respect to limit of detection(LOD), limit of quantification(LOQ), exactness, reproducibility, ruggedness and robustness. The LOD, LOQ values of metabisulfite were 0.3PPM and 1.0PPM respectively.