N-Phthalimido β-amino acid derivatives, 3-phthalimido-3(2-hydroxyphenyl) propanoic acid (P2HPA) and 3-phthalimido-3(2-nitrophenyl) propanoic acid (P2NPA) with new series of di- and triorganotin(IV) complexes (1-12) have been designed and synthesized. All the ligands and organotin(IV) complexes were characterized by elemental analysis, Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H, 13C, 119Sn) spectroscopy and electron ionization mass spectrometry (EI-MS). Synthesized ligands and complexes were screened to determine the antibacterial activity and results showed that the triorganotin(IV) complexes have better activity compared to diorganotin(IV) complexes and ligands. In addition, molecular docking analysis of ligands on the catalytic pocket of sortase A (PDB ID 1T2W) showed that the ligands can bind the active amino acid residues in the pocket. The antioxidant activity was also performed by the DPPH (1,1-diphenyl-2-picrylhydrazyl radical) method and complexes showed better results than ligands. The compounds were also tested in vivo to determine the hypoglycemic activities on different groups of alloxan induced diabetic rabbits. The complexes (1-6) were found better hypoglycemic agents as they stabilized the glucose level to about 175-105 mg dL-1 as compared to ligand P2HPA.

ABSTRACT A simple and isocratic HPLC method with stability indicating nature was developed and then subsequently validated for simultaneous determination of ciprofloxacin and dexamethasone in pharmaceutical formulations, human serum and urine. Best chromatographic separations were attained within run time of 10 minutes using C8 as stationary phase and mixture of phosphate buffer and methanol (41:59 v/v) as mobile phase. The mobile phase was flowed at 1.5 mL min−1 with detection of both the analytes at 270 nm using photodiode array detector. Validation of the method was accomplished using specificity, linearity, accuracy, precision, robustness, LOD and LOQ. The method was found linear from 3-21 mg mL−1 for ciprofloxacin (r2 ≥ 0.999) and 1-7 mg mL−1 for dexamethasone (r2 ≥ 0.999). The %age recoveries of ciprofloxacin in spiked human urine and serum were ≥99% and ≥85% respectively, while for dexamethasone they were ≥97% in both matrices. The method proficiently separated the peaks of ciprofloxacin and dexamethasone from all types of interfering substances including degradation products/impurities with purity index ≥ 0.9998. The method thus was stability-indicating and can be employed for simultaneous analysis of ciprofloxacin and dexamethasone in complex matrices involving multiple components in the mixture.

Abstract In this study, conditions were optimized for development of a simple RP-HPLC method for simultaneous analysis of gatifloxacin and dexamethasone in different matrices like pharmaceuticals, human serum and urine. Good separation of gatifloxacin and dexamethasone from the induced degradation products was accomplished using C8 as stationary phase; 0.02 M phosphate buffer (pH 3.0) and methanol (42:58 v/v) as mobile phase. The concentration was measured with DAD at 270 nm. Linearity was observed in the range of 0.000040-0.000280 mol/L for gatifloxacin (r2≥0.999) and 0.000013-0.000091 mol/L for dexamethasone (r2≥0.999). Both the analyte peaks were completely separated from the peaks of induced degradation products as indicated by the peak purity index (≥0.9999 for both analytes). The optimized method is recommended to be used for concurrent analysis of gatifloxacin and dexamethasone in different matrices.

A bioactive N,N-diacetylglycine (NNDAG) and new organotin(IV) complexes (OTCs) (1-7) were synthesized. Spectroscopic techniques were employed to characterize NNDAG and OTCs. FTIR was employed to verify N,N protection of glycine by acetyl groups. The disappearance of υ(OH) at 3000-2600 cm-1 showed de-protonation of free ligand. The Δυ 150<200 cm-1 of OTCs 4-7 verified bidentate coordination with tetrahedral geometry. The Δυ of OTCs1 and 3 was <200 cm-1 exhibitingtrans -octahedral geometry while OTC 2 dimer was assigned a unique sinusoidal view. The 1H NMR spectra of OTCs verified their synthesis by de-protonation of NNDAG and no chemical shift was found downfield for carboxylic acid proton. The 13C, 119Sn NMR and Mass spectrometric data also supported FTIR and 1H NMR descriptions. The OTCs 4, 5, 6 and7 (500 ppm) proved twice as active against Escherichia coli as the standard antibiotic enoxacin (1000 ppm). The promising property of the OTCs (4, 5, 6 and7) is clearly due to their tetrahedral. The OTCs 4and 5 exhibited excellent activity against M. minimum and good activity against T. castaneum.LD50 of all the compounds were determined and OTCs4, 5 and 7 were found to be active.

A diacereína é usada para o alívio sintomático e para a regeneração da cartilagem na osteoartrite. Devido aos efeitos adversos gastrointestinais, baixa solubilidade aquosa e biodisponibilidade, o seu uso clínico tem sido restrito. O objetivo do presente estudo foi melhorar o perfil de dissolução deste fármaco e obter liberação prolongada através do planejamento de um novo sistema de liberação designado de niossoma. Cinco formulações distintas de niossomas (F1 a F5) contendo tensoativos não iônicos (monoestearato de sorbitano) e colesterol, em diferentes proporções, de 5:5, 6:4, 7:3, 8:2 e 9:1, foram desenvolvidas através da técnica de evaporacão de fase reversa. Os tamanhos e índices de polidispersibilidade (PDI) obtidos variam entre 0,608 e 1,01 µm e entre 0,409 e 0,7781, respectivamente. Imagens de microscopia electrônica de varrimento (SEM) da formulação selecionada (F3) revelaram vesículas esféricas. Obteve-se encapsulação de 79,8% com a formulação F3 (7:3). Estudos de dissolução usando o método de diálise demonstraram padrão de liberacão prolongada para todas as formulações. A proporção de tensoativo e colesterol (7:3) na formulacão F3 prolongou o tempo de liberação do fármaco (T50%) até 10 horas. Estudos de modelação cinética demonstraram ordem de liberacão zero (R2=0,9834) e o expoente de liberação "n" do modelo de Korsmayer-Peppas (n=0.90) confirmou a liberação não-fickiana e anômala. Os resultados deste estudo sugerem que a diacereína pode ser encapsulada com sucesso no interior de niossomas, utilizando monostearato de sorbitano, o qual tem potencial para liberar, eficientemente, a diacereína no local de absorção.

Diacerein is used for symptomatic relief and cartilage regeneration in osteoarthritis. Due to gastrointestinal side effects, poor aqueous solubility and low bioavailability, its clinical usage has been restricted. The objective of the present study was to enhance its dissolution profile and to attain sustained release by designing a novel delivery system based on niosomes. Five niosomal formulations (F1-F5) with non-ionic surfactant (sorbitan monostearate) and cholesterol in varying ratios of 5:5, 6:4, 7:3, 8:2 and 9:1 were developed by the reverse-phase evaporation technique. The size and polydispersivity index (PDI) were found in the range of 0.608 µm to 1.010 µm and 0.409 to 0.781, respectively. Scanning electron microscopy (SEM) of the selected formulation (F3) revealed spherical vesicles, and 79.8% entrapment was achieved with F3 (7:3). Dissolution studies using the dialysis method showed sustained release behaviour for all formulations. The optimized surfactant-to-cholesterol concentration (7:3) in formulation F3sustained the drug-release time (T50%) up to 10 hours. Kinetic modelling exhibited a zero-order release (R2=0.9834) and the release exponent 'n' of the Korsmayer-Peppas model (n=0.90) confirmed non-fickian and anomalous release. The results of this study suggest that diacerein can be successfully entrapped into niosomes using sorbitan monostearate and that these niosomes have the potential to deliver diacerein efficiently at the absorption site.

A simple, specific and accurate stability indicating RP-HPLC method was developed for the determination of acetaminophen, pamabrom and pyrilamine maleate simultaneously in pharmaceutical dosage forms. Successful separation of all the components was enacted within 10 min using C18 column with mobile phase of methanol and acidified water (pH 1.8) in the ratio of (27: 73 v/v respectively). Flow rate of the mobile phase was 1.5 mL/min with detection at 300 nm. The method was validated in accordance with ICH guidelines. Response was a linear function of concentration over the range of 50- 150 μg/mL for acetaminophen, 2.5-7.5 μg/mL for pamabrom and 1.5-4.5 μg/mL for pyrilamine maleate. The method resulted in excellent separation of all the analytes along with their stress induced degradation products with acceptable peak tailing and good resolution. It is therefore can be applied successfully for simultaneous determination of acetaminophen, pamabrom and pyrilamine maleate in pharmaceutical formulations and their stability studies.

Se ha desarrollado un procedimiento simple y específico procedimiento para la determinación de acetaminofeno, pamabrom y maleato de pirilamina en formulaciones farmacéuticas por HPLC en fase inversa. La separación de todos los componentes se obtuvo en 10 min utilizando una columna C18 y la fase móvil compuesta por metanol y solución acuosa a pH 1.8 (con ácido sulfúrico) en relación 27: 73 v/v. La velocidad del flujo en la columna fue de 1.5 mL/min y la detección espectrofotométrica en 300 nm. El método fue validado siguiendo los criterios ICH. La respuesta fue lineal en el intervalo de concentraciones 50- 150 μg/mL para acetaminofeno, 2.5-7.5 μg/mL para pamabrom y 1.5-4.5 μg/mL para maleato de pirilamina. El procedimiento permitió la separación de los tres analitos y de sus productos de degradación inducidos en condiciones de estrés con aceptable simetría de picos y resolución cromatográfica. Es por ello que este procedimiento puede ser empleado para la determinación de acetaminofeno, pamabrom y maleato de pirilamina en formulaciones farmacéuticas y en estudios de su estabilidad.

Utilizou-se abordagem de viabilidade custo-efetividade e isocrática, baseada em CLAE, empregando coluna C-18 (250 mm x 4,6 mm, 5 µm) para separar e avaliar os fármacos, rosuvastatina, anlodipino e seus produtos de degradação induzida por estresse, simultaneamente, em formulações farmacêuticas. Focada nos parâmetros das diretrizes da ICH, a separação eficiente de ambos os fármacos e de seus produtos de degradação foi obtida por meio da otimização da fase móvel com mistura de solventes 30:70 (v/v), respectivamente, acetonitrila e tampão acetato de amônio O,1 M (pH 5). A velocidade de fluxo da fase móvel foi de 1,5 mL/min e todas as detecções foram realizadas em 240 nm, utilizando detector de UV. O método foi linear no intervalo de concentração de 1-200 µg/mL para a rosuvastatina com coeficiente de determinação 0,996. Para o anlodipino, a linearidade ficou na faixa de 0.5-100 µg/mL, com coeficiente de determinação 0,994. Ambos os fármacos, junto com seus produtos de degradação, foram separados em menos de vinte minutos. Os resultados de precisão intra-dia e inter-dia variaram de 0,72 a 1,81% para a rosuvastatina e de 0,83 a 1,88%, para o anlodipino. Os resultados mostram que este método validado pelo ICH pode ser empregado com sucesso tanto para a rotina quanto para a quantificação simultânea da estabilidade de ambos os ingredientes ativos em formulações farmacêuticas.

A viable cost-effective and isocratic approach employing C-18 column (250 mm × 4.6 mm, 5 µm) based HPLC has been utilized to separate and estimate the drugs, rosuvastatin, amlodipine and their stress induced degradation products, simultaneously in pharmaceutical formulations. Focused on ICH guideline parameters, the efficient separation of both drugs and their degradation products was achieved by optimizing a 30:70 (v/v) solvent mixture of acetonitrile and 0.1 M ammonium acetate buffer (pH 5) as mobile phase. The flow rate of the mobile phase was 1.5 mL/min and all the detections were carried out at 240 nm using UV detector. The method was linear in the concentration range of 1-200 µg/mL for rosuvastatin with 0.996 coefficient of determination value. For amlodipine, linearity was in the range of 0.5-100 µg/ml with 0.994 coefficient of determination value. Both the drugs along with their degradation products were separated in less than twenty minutes. The results of within-day and between-day precision were varied from 0.72 to 1.81% for rosuvastatin and 0.83 to 1.88% for amlodipine. The results show that this ICH validated method can be employed successfully for the routine as well as stability quantification of both the active ingredients simultaneously in pharmaceutical formulations.

A stability-indicating RP-HPLC method is presented for determination of gatifloxacin and flurbiprofen in binary combination. Gatifloxacin, flurbiprofen and their degradation products were detected at 254 nm using a BDS Hypersil C8 (250 X 4.6 mm, 5 µm) column and mixture of 20 mM phosphate buffer (pH 3.0) and methanol 30:70 v/v as mobile phase. Response was linear over the range of 15-105 mg mL-1 for gatifloxacin (r² > 0.998) and of 1.5-10.5 mg mL-1 for flurbiprofen (r² > 0.999). The developed method efficiently separated the analytical peaks from degradation products (peak purity index > 0.9999). The method developed can be applied successfully for determination of gatifloxacin and flurbiprofen in human serum, urine, pharmaceutical formulations, and their stability studies.

A simple, precise, sensitive and validated reverse-phase high performance liquid chromatographic (RP-HPLC) method was developed for the simultaneous estimation of rosuvastatin and ezetimibe in human plasma. The method involved protein precipitation and extraction of both drugs from plasma using acetonitrile and then separation on a C-18 column. Both the analytes were detected at a wavelength of 240 nm using diode array detector. Mobile phase for the said separation consists of a mixture of 1.5% phosphoric acid and acetonitrile in 30:70, v/v ratio. Linearity was in the range of 0.32-267 mg/mL for rosuvastatin and 0.08-67 mg/mL for ezetimibe with coefficient of determination between 0.9997 and 0.9967. Limit of detection was 0.106 μg/mL for rosuvastatin and 0.026 mg/mL for ezetimibe whereas limit of quantification was 0.32 mg/mL and 0.08 mg/mL for rosuvastatin and ezetimibe respectively. Recovery of both the analytes was greater than 75% with RSD less than 15 %. The total run time was less than five min for the two components. The developed method can be fruitfully employed for the determination of these two drugs in human plasma.

O presente estudo descreve o desenvolvimento e a subsequente validação de indicador de estabilidade simples e acurada por RP-HPLC para a determinação de esparfloxacino e dexametasona em formulações farmacêuticas na presença de produtos de degradação induzidos por estresse. Tanto os fármacos quanto os produtos de degradação induzidos pelo estresse foram separados em 10 minutos, utilizando coluna C8 e mistura de methanol e tampão fosfato 0,02 M, pH 3,0 (60:40 v/v, respectivamente) como fase móvel e detector de arranjo de diodo a 270 nm, A análise de regressão mostrou linearidade na faixa de 15-105 µg/mL para esparfloxacino e 5-35 µg/mL para a dexametsona. Todos os analitos foram resolvidos adequadamente com tailing aceitável. O pico de pureza dos dois foi maior que 0.9999, não mostrando picos de co-eluição. O método desenvolvido foi aplicado para a determinação simultânea de esparfloxacino e dexametasona em formulações farmacêuticas e para estudos de estabilidade.

The present study describes the development and subsequent validation of simple and accurate stability indicating RP-HPLC method for the determination of sparfloxacin and dexamethasone in pharmaceutical formulations in the presence of their stress-induced degradation products. Both the drugs and their stress-induced degradation products were separated within 10 minutes using C8 column and mixture of methanol and 0.02 M phosphate buffer pH 3.0 (60:40 v/v, respectively) as mobile phase at 270 nm using diode array detector. Regression analysis showed linearity in the range of 15-105 µg/mL for sparfloxacin and 5-35 µg/mL for dexamethasone. All the analytes were adequately resolved with acceptable tailing. Peak purity of the two drugs was also greater than 0.9999, showing no co-elution peaks. The developed method was applied for simultaneous determination of sparfloxacin and dexamethasone in pharmaceutical formulations for stability studies.

A simple, RP-HPLC method was established for determining moxifloxacin and ketorolac in pharmaceutical formulations. Moxifloxacin, ketorolac and their degradation products were separated using C8 column with methanol and phosphate buffer pH 3.0 (55:45 v/v) as the mobile phase. Detection was performed at 243 nm using a diode array detector. The method was validated using ICH guidelines and was linear in the range 20-140 µg mL-1 for both analytes. Good separation of both the analytes and their degradation products was achieved using this method. The developed method can be applied successfully for the determination of moxifloxacin and ketorolac.

The present study reports the development and validation of a simple, economic and sensitive HPLC method for the concurrent determination of naproxen and esomeprazole in pharmaceutical formulations. Isocratic chromatography was performed with C-18 column and mixture of phosphate buffer (pH 6.1) and acetonitrile in ratio of (40:60, v/v) at 1.5 mlmin-1. The eluents were monitored at 302 nm using UV detector. The method was isocratic in the range of 9.38 to 300 µgml-1 for naproxen and 0.5 to 16 µgml-1 for esomeprazole. Validation of the method was performed by testing parameters like linearity, accuracy, precision, robustness, specificity, LOD and LOQ values. In the specificity the drugs were subjected to forced degradation studies like acidic, basic, oxidative and thermal stresses. Both the analytes were separated within three minutes. As the method separates the degradation products produced during forced degradation studies from the active analytes so it can be used not only for regular determination of naproxen and esomeprazole but also for their stability studies.

In the present study conditions were optimized for the development and validation of a simple, sensitive and isocratic reverse phase high performance liquid chromatographic method for the simultaneous determination of ezetimibe and lovastatin in human plasma using gemfibrozil as internal standard. After a single step extraction with acetonitrile, satisfactory elution of both the analytes along with internal standard was achieved on a Merck C-18 column using a mixture of 0.1 M ammonium acetate pH 5.0 and acetonitrile in the ratio of (28:72, v/v) at a flow rate of 1.5 ml/min. The detection was carried out at a wavelength of 240 nm using a photodiode array detector. The method was linear in the concentration range of 0.2-25 |xg/ml for ezetimibe and 0.4-50 |xg/ml for lovastatin. The extraction recovery of analytes was greater than 85 % and within day and between day precision was also satisfactory. The method was validated by performing its linearity, recovery, precision, LOD/LOQ values and stability of solutions. The total eluting time for the analysis is less than twelve minutes. As the plasma peaks did not interfere with the peaks of analytes so the method can be used for the determination of ezetimibe and lovastatin in human plasma and may possibly be for the pharmacokinetic study.

Seis novos ésteres diorganoestanho(IV) com composição geral R2SnL2 (onde R: Me(1), Et(2), Pr(3), Bu(4), Ph(5), Bz(6) e L(7): ácido p-N-maleimidobenzóico) foram sintetizados neste trabalho. Espectros de absorção no infravermelho e de Mössbauer de 119mSn no estado sólido revelaram o comportamento bidentado de L em relação ao centro diorganoestanho(IV) nos complexos octaédricos distorcidos. Espectros de RMN de ¹H, 13C e 119Sn, em CDCl3, indicaram hexacoordenação em 1-4, pentacoordenação de 5 em geometria trapezoidal distorcida, e ausência de hipercoordenação no arranjo tetraédrico em 6. Dados de análise elementar comprovaram a estequiometria dos compostos organoestanho(IV). Foram realizados testes in vitro contra cinco espécies de Leishmania: L. major, L. tropica, L. infantum, L. mex. mex. e L. donovani. Resultados promissores foram observados e, com base nos dados obtidos nesses ensaios, tentou-se estabelecer relações estrutura-atividade. O aumento no tamanho dos grupos R em {R2SnIV}2+ aumentou a lipofilicidade dos complexos organoestanho(IV), acentuando assim a atividade antileishmania.

Six new diorganotin(IV) esters with the general composition R2SnL2 (where R: Me(1), Et(2), Pr(3), Bu(4), Ph(5), Bz(6) and L(7): p-N-maleimido-benzoic acid) have been synthesized. Solid state FTIR and 119mSn Mössbauer spectra revealed bidentate behavior of L towards the diorganotin(IV) centre in the distorted octahedral products. ¹H, 13C and 119Sn NMR spectra in CDCl3 indicated hexacoordination in 1-4, penta-coordination of 5 in skew-trapezoidal geometry, and absence of hypercoordination in tetrahedral 6. Elemental analyses data have been found to corroborate the stoichiometry of the title organotin(IV) compounds. In vitro anti-leishmanial screenings have been conducted on five leishmanial strains of L. major, L. tropica, L. infantum, L. mex. mex. and L. donovani. Promising results have been observed and, on the basis of the data obtained during these assays, a structure-activity relationship has been suggested. The increasing size of the R groups in the {R2SnIV}2+ moieties increased the lipophilicity of organotin(IV) complexes, which thereby enhanced the anti-leishmanial activity.

A simple, sensitive and isocratic reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed for the simultaneous determination of olmesartan medoxomil and amlodipine in pharmaceutical tablet formulations. HPLC analysis was carried out using reverse phase isocratic elution with aC18 column and amobilephase of 0.05 Mammonium acetate pH 6.8 and acetonitrile intheratio of 40:60, v/v. Detection of the analytes was achieved using UV detector at 239 nm. The retention times of olmesartan medoxomil and amlodipine were 2.50 and 3.94 respectively Linearity of the method was found to be in the concentration range of 16-112 µgml-1 for olmesartan medoximil and 4-28 µgml-1 for amlodipine. The correlation coefficient value was greaterthan 0.9999 for both the analytes. The method is suitable for the estimation of both the components simultaneously in pharmaceutical tablet formulations.