Simultaneous Quantification of Mesalamine and Its Metabolite N-Acetyl Mesalamine in Human Plasma by LC-MS/MS and Its Application to a Bioequivalence Study.

Liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used for simultaneous quantification of mesalamine and its metabolite N-acetyl mesalamine in human plasma with N-acetyl mesalamine D3 as an internal standard (IS). Chromatographic separation was performed on a Thermo, HyPURITY C18 (150 x 4.6 mm, 5 m) column with an isocratic mobile phase composed of 10 mM ammonium acetate and methanol in the ratio of 85:15 (%v/v), at the flowrate of 0.6 mL/min. The drug, metabolite and internal standard were extracted by liquid-liquid extraction. The method was validated over a linear concentration range of 2-1500 ng/mL for mesalamine and 10- 2000 ng/ml for N-acetyl mesalamine, which demonstrated intra and inter-day precision ranging from 1.60 to 8.63% and 2.14 to 8.67% for mesalamine and 0.99 to 5.67% and 1.72 to 4.89% for N-acetyl mesalamine respectively. Similarly, the intra- and inter-day accuracy varied from 102.70 to 105.48% and 100.64 to 103.87% for mesalamine, 99.64 to 106.22% and 100.71 to 104.27% for N-acetyl mesalamine respectively. Both analytes were found to be stable throughout freeze–thawing cycles, bench top and postoperative stability studies. The method was successfully applied to support a bioequivalance study of healthy subjects.

Comparative in vivo evaluation of three types of honey on topical wound healing activity in rabbits.

The present investigation has focused on the comparative evaluation of topical wound healing activity in rabbits using three types of honeys such as Sidr (SDH), Thyme (TYH), Spring (SPH). The activity was compared with commercial wound healing formulations, Mebo (MBC) and Fusidin (FSC) creams. Among the different types of the honey SDH was found to possess higher healing rate of wounds induced either by thermal or chemical methods. Whereas, in thermal induced burns, both TYH and SPH have shown similar wound healing activity but better than that of standard drugs. The activity for thermal and chemical induced burns was found in the order of SDH > TYH/SPH > MBC > control and SDH > TYH > SPH > FSC > control respectively. Among the three tested honeys, the t-test data was compared to those of controls and it was found that there was a significant (p<0.05) reduction in the wound area. It was concluded that honey in general could be employed as natural topical wound healing agent comparable to commercial synthetic analogs tested in the study. Further the present investigation proves that SDH is possessing superior wound healing activity than that of TYH and SPH.

Influence of Sodium CMC and HPMC on the Physical Characteristics of Ofloxacin Floating Matrix Tablets.

Aims: Sustained release floating drug delivery systems or gastro retentive drug delivery systems enables prolonged and continuous input of drug to the upper part of gastrointestinal tract and improves the bioavailability of medication. A new strategy is proposed for the development of floating drug delivery systems of Fluoroquinolone antibiotic, Ofloxacin, a potent moiety for treating UTI’s. Methodology: Various rate retarding polymers like HPMC K4M, HPMC 5 cps and swelling agent as Sodium carboxymethyl cellulose in different proportions were tried and optimized to achieve the drug release for 8 hr. All the formulations were evaluated for floating properties, swelling characteristics and in vitro drug release studies. The in vitro drug release was found to be matrix diffusion controlled. Optimized formulation was subjected to intermediate stability studies at various combinations of temperature and humidity according to ICH guidelines. Results: Lower hardness and higher thickness decreased the floating lag time and increased floating duration. Based on drug release studies, formulation F5 was optimized as the best formulation because it released about 89.27 ±2.6% of the drug at the end of 8 hr while other formulations released not more than 80 ±2.2%. This may be due to high NaCMC content which might have caused excessive channeling, thereby giving a burst release. Optimized formulation F5 was found to follow zero order kinetics with r2 value of 0.993. Conclusion: In conclusion we have been proved that HPMC K4M has retarded the drug release, while HPMC 5cps has facilitated high buoyancy time for the tablets. NaCMC has influenced as channeling agent. Formulation F5 was optimized for its long buoyancy time, prolonged duration of drug release, zero order and diffusion controlled drug release kinetics which can assure 100% bioavailability.

Design of dissolution media for in-vitro bioequivalence testing of Lamivudine.

The present investigation is aimed at developing the stability indicating dissolution media for the determination of lamivudine (3TC) in pharmaceutical dosage forms. The stability of 3TC was tested in various dissolution media maintained at ambient temperature and 37 oC for 48 hrs. Stability studies of 3TC in various media indicated that the drug was stable in 0.1M HCl, pH 1.2 KCl-HCl buffer, pH 6.2 and pH 7.0 phosphate buffers. The λmax were found to be 280.0, 278.8, 273.0 and 271.5nm for 0.1M HCl, pH 1.2 KCl-HCl buffer, pH 6.2 and pH 7.0 phosphate buffers respectively with low CV of <4.44%. The linearity of standard plots in optimized media was 0.5-40 μg/ml for 0.1M HCl and pH 1.2 KCl-HCl buffer. Similarly it was 0.5-60 μg/ml in pH 6.2 buffer and 0.2-40 μg/ml in pH 7.0 phosphate buffer. The validated methods were applied to determine 3TC concentration in formulations. In-vitro dissolution testing indicated that the 3TC was stable and drug release is uniform from tablet dosage forms. The optimized media could be employed to study the dissolution profiles of 3TC in bioequivalence studies.

Pharmacognostical studies on the leaves of Ficus altissima blume.

Ficus altissima Blume belonging to family Moraceae is perennial tree with 20-30 ft tall distributed in the hills of northern India and deccan peninsula, up to an altitude of 100-2000 m. It is commonly known as Council Tree. Leaves and bark are used in skin diseases. The tree is one of the recorded hosts of the Indian lac insect and is a source of red colour. Owing to its unexplored medicinal importance, the macroscopic and the microscopic characters of the leaves were studied which will serve as reference standard in identification of the tree.

Erythrocytes as carrier for drugs, enzymes and peptides.

Erythrocytes are potential biocompatible carriers for different drugs, peptide molecules and different enzymes. Now a day the method that is used for encapsulation of pharmaceuticals into the erythrocytes mainly based on the hypo-osmotic dialysis. Encapsulation of these drugs or enzymes or peptides into erythrocytes significantly changes the pharmacokinetic properties of drugs in both animals and humans, enhancing liver and spleen uptake and targeting the reticuloendothelial system. By the encapsulation of these into erythrocytes can be applied as targeted drug delivery systems. Erythrocytes are successful as carrier systems for different drugs, enzymes and peptide molecules. The result after using drug encapsulated in erythrocytes is more compared to the free form of the drug.

Method development and validation for naratriptan determination in human plasma by HPLC with tandem mass spectrometry detection, and its application to bioequivalence study / Desenvolvimento de método e validação para determinação de naratriptan em plasma humano por HPLC com detecção de espectrometria de massa em tandem, e sua aplicação ao estudo de bioequivalência

The authors developed a simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of naratriptan (NP) in human plasma using naratriptan-d3 (NPD3) as an internal standard (IS). Chromatographic separation was performed on a Zorbax SB-C18, 75 x 4.6 mm, 3.5 µm column with an isocratic mobile phase composed of 0.1 percent formic acid : acetonitrile (50:50 v/v), at a flow-rate of 0.6 mL/min. NP and NPD3 were detected with proton adducts at m/z 336.5→98.0 and 339.4→101.0 in selected reaction monitoring (SRM) positive mode, respectively. The liquid-liquid extraction method was used to extract the NP and NPD3. This method was validated over a linear concentration range of 0.1-25.0 ng/mL with a correlation coefficient of (r2) > 0.9998. The Intra-day and Interday precision was found to be 1.8 to 3.6 percent, and 2.3 to 2.6 percent, and accuracy to be 101.7- 104.2 percent and 101.8 to 102.9 percent, respectively. NP was found to be stable throughout freeze-thaw (three cycles), bench top and auto sampler stability studies. This method was successfully applied for the analysis of plasma samples following oral administration of NP (2.5 mg) in 31 healthy Indian male human volunteers under fasting conditions.

Os autores desenvolveram um método simples, sensível e específico de cromatografia líquida-espectrometria de massa-tandem (LC-MS/MS) para a quantificação de naratriptan (NP) em plasma humano empregando naratriptan-d3 (NPD3) como padrão interno de referência (IS). A separação cromatográfica foi realizada em coluna Zorbax SB-C18, 75 x 4,6 mm, 3,5 μm com fase móvel isocrática composta por 0,1 por cento ácido fórmico : acetronitrila (50:50 v/v) e taxa de fluxo de 0,6 mL/min. NP e NPD3 foram detectados com adutos de prótons a m/z 336.5→98.0 e 339.4→101.0 in em modo positivo do tipo monitoramento de reação selecionada (SRM), respectivamente. Extração líquido-líquido foi empregada para extrair NP e NPD3, sendo o método validado para uma faixa linear de concentração de 0,1-25,0 ng/mL resultando em coeficiente de correlação (r2) > 0,9998. A variação intra e interdia observada para precisão foi de 1,8 a 3,6 por cento e 2,3 a 2,6 por cento, respectivamente; para exatidão a variação foi de 101,7 a 104,2 por cento e 101,8 a 102,9 por cento, respectivamente. O NP se mostrou estável frente a processos de congelamento-descongelamento (3 ciclos), e estudos de estabilidade de bancada e amostragem automática. O método desenvolvido foi aplicado com sucesso para a análise de amostras de plasma após a administração oral de 2,5 mg de NP em 31 voluntários humanos, de nacionalidade indiana, sexo masculino, sob condições aceleradas.