K. Vyas

Novel D-ring analogues of podophyllotoxin as potent anti-cancer agents ☆

Several D-ring modified analogues of podophyllotoxin were prepared viz semi-synthesis starting from naturally occurring podophyllotoxin and determined their in vitro anti-cancer activity. Most of the analogues have shown good activity towards human cancer cell lines.

LC method for the determination of assay and purity of sibutramine hydrochloride and its enantiomers by chiral chromatography.

Two isocratic liquid chromatography (LC) methods have been developed for the purity estimation and quantitative determination of sibutramine HCl, using 4-chloro aniline and lovastatin as internal standards, respectively. The precision has been checked in terms of F-test variance ratio using latter method as reference. The ratio of variances of the two methods is close to unity, confirming their good precision. The correlation coefficient for linear regression is more than 0.999. The inter and intra-day precision is found to be < 1.3% RSD. The accuracy determined as relative mean error (RME) for the intra-day assay is +/- 1.7%. The enantiomeric separation of sibutramine by chiral chromatography method has been described also. This method is capable of separating the two enantiomers with a selectivity of 1.4 and a resolution of 4.0. Both methods are found to be stability indicating and useful in the quality control of the bulk material.

Tandem C–C coupling – intramolecular acetylenic Schmidt reaction under Pd/C–Cu catalysis

A new one-pot reaction for the regioselective construction of a six-membered fused N-heterocyclic ring leading to isoquinolones under Pd/C-Cu catalysis is described.

Sparfloxacin, an antibacterial drug

The title compound, sparfloxacin or cis-5-amino-1-cyclopropyl-7-(3,5-dimethylpiperazin-1-yl)-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid trihydrate, C(19)H(22)F(2)N(4)O(3).3H(2)O, is an antibacterial drug. The molecule, which crystallizes as a trihydrate, is in the zwitterionic form in the solid state. Hydrogen bonds stabilize the molecules in the lattice.

Isolation and characterization of process-related impurities in linezolid.

Two unknown impurities in linezolid bulk drug at levels below 0.1% (ranging from 0.05 to 0.1%) were detected by a simple isocratic reverse phase high performance liquid chromatography (HPLC). These impurities were isolated from crude sample of linezolid using reverse phase preparative HPLC. Based on the spectroscopic data (IR, NMR and MS) the structures of the impurities were characterized as (S)-N-[[-(3-(3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl] acetate(I) and (S)-N-[[-(3-(3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl] chloride(II). The synthesis from an unambiguous route and the formation of impurities was discussed.

Impurity profile study of repaglinide.

Three unknown impurities and a byproduct in repaglinide 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) method. These impurities were isolated from crude sample of repaglinide using reversed-phase preparative high performance liquid chromatography. Based on the spectroscopic data (IR, NMR and MS) the structures of these impurities (I, II and IV) and byproduct (III) were characterised as 4-carboxymethyl-2-ethoxy-benzoic acid (I), 4-cyclohexylaminocarbamoylmethyl-2-ethoxy-benzoic acid (II), 1-cyclohexyl-3-[3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl]-urea (IV) and 1,3-dicyclohexyl urea (III), respectively. Their synthesis and formation is discussed.

Identification of degradation products in stressed tablets of Rabeprazole sodium by HPLC‐hyphenated techniques

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) 0.17, 0.22 and 0.28. The Impurity‐I (0.17 RRT) was isolated using preparative HPLC and characterized by NMR and MS. The other two impurities, Impurity‐II (RRT 0.22) and Impurity‐III (RRT 0.28) could not be isolated, hence they are characterized by HPLC‐hyphenated techniques, LC–NMR and high‐resolution LC–MS. On the basis of the spectral data, the Impurity‐I, Impurity‐II and Impurity‐III were characterized as 1‐(1H‐benzo[d]imidazol‐2‐yl)‐3‐methyl‐4‐oxo‐1,4‐dihydropyridine‐2‐carboxylic acid, 1H‐benzo [d] imidazole‐2‐sulfonic acid and 4‐(3‐methoxy propoxy)‐3‐methyl‐2‐pyridine carboxylic acid, respectively. Copyright

Solid state structural studies of saccharin salts with some heterocyclic bases

Five saccharin salts with heterocyclic bases 1,2-bis(4-pyridyl)ethane, 1; trans-1,2-bis(4-pyridyl)ethylene, 2; piperazine, 3; 1,4-dimethylpiperazine, 4 and 2,2′-dipyridylamine, 5 have been synthesized and characterized by single crystal X-ray diffraction. The crystal structures reveal that in all the salts, the hydrogen atom has been transferred from saccharin nitrogen to the base nitrogen and sustained through charge-assisted hydrogen bonds. In salts 1–3, N+–H donor forms N+–H⋯O hydrogen bonds with the carbonyl oxygen of saccharinate, whereas it forms N+–H⋯N− in 4 and intramolecular N+–H⋯N in 5. Salts 2 and 3 also form weak N+–H⋯N−hydrogen bonds. Only in salt3, the SO2 moiety is involved in conventional hydrogen bonding.

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.