M. Saeed Arayne

Spectrophotometric determination of gabapentin in pharmaceutical formulations using ninhydrin and π-acceptors

Simple, rapid and sensitive spectrophotometric procedures are developed for the analysis of gabapentin in pure form as well as in their pharmaceutical formulations. The methods are based on the reaction of gabapentin as n-electron donor with ninhydrin and pi-acceptors namely, 2,3,5,6-tetrachloro-1,4-benzoquinone, chloranilic acid, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, tetracyanoethylene and 7,7,8,8-tetracyanoquinodimethane. The obtained complexes were measured at 568, 230, 314, 304, 335 and 439 nm for ninhydrin, chloranil, Chloranilic acid, DDQ, TCNE and TCNQ respectively. The proposed procedures could be successfully applied to the determination of gabepentin with good recovery; percent ranged from 99.3 to 100.7 The association constants and free energy changes using Benesi-Hildebrand plots are also studied.

RP-HPLC Method for Simultaneous Determination of Captopril and Diuretics: Application in Pharmaceutical Dosage Forms and Human Serum

An isocratic reversed phase high-performance liquid chromatographic (RP-HPLC) method has been developed for the simultaneous determination of captopril and diuretics (furosemide and hydrochlorothiazide) in API, dosage formulations and human serum. Chromatographic separation was achieved on Purospher Start C18 (250 mm x 4.6 mm, 5 μm) and Hypersil ODS C18 (150×4.6mm, 5micron) columns using mobile phase, methanol: water (70:30 v/v) adjusted to pH 3.0 via phosphoric acid 85% having flow rate of 1.0 mL min -1 at ambient temperature with detector set at 225 nm. Calibration curves were linear over range of 5-25 μg mL -1 with a correlation coefficient ± 0.999. LOD and LOQ were in the ranges of 0.4-2.3 μg mL -1 . Intra and inter-run precision and accuracy results were 98.0 to 102%.

SIMULTANEOUS DETERMINATION OF CEFTRIAXONE SODIUM AND STATIN DRUGS IN PHARMACEUTICAL FORMULATIONS AND HUMAN SERUM BY RP-HPLC

An accurate, sensitive and least time consuming reverse phase high performance liquid chromatographic (RP-HPLC) method for the estimation of ceftriaxone in the presence of statin drugs in formulation and human serum has been developed and validated. Chromatographic separation was conducted on prepacked Purospher Star, C18 (5 mm, 250 x 4.6 mm) column at room temperature using methanol:water:acetonitrile (70:15:20 v/v/v) as a mobile phase, pH adjusted at 2.8 with ortho-phosphoric acid and at a flow rate of 1.0 mL/minute, while UV detection was performed at 240 nm. The results obtained showed a good agreement with the declared content. The method shows good linearity in the range of 2.5–25 µg/mL with a correlation coefficient 0.9966 – 0.9998 (inter-and intra-day RSD 98.72 %. The proposed method may be used for the quantitative analysis of commonly administered statin’s i.e. simvastatin, rosuvastatin atorvastatin and pravastatin alone or in combination with ceftriaxone from raw materials, dosage formulations and in serum. The established HPLC method is rapid, accurate and selective, because of its sensitivity and reproducibility.

RP-HPLC Method for the Simultaneous Determination of Captopril andH2-Receptor Antagonist: Application to Interaction Studies

Rapid, sensitive, simple and accurate high-performance liquid chromatographic (HPLC) method is developed and validated for the simultaneous determination of captopril with H2 receptor antagonists as cimetidine, ranitidine and famotidine. Captopril was separated from H2 receptor antagonist using pre packed Purospher star C18 (5 μm, 25×0.46 cm) column methanol: water (60:40 v/v) were used as the mobile phase, pH 3.0 ± 0.02 was adjusted by orthophosphoric acid. The flow rate was 0.8 mLmin-1 at ambient temperature, diluent was 50:50 methanol water while UV detection was performed at 225 nm. The retention time for captopril was found to be 5.2 minute, for ranitidine and famotidine 2.5 minute and cimetidine 2.7 minute. Each drug showed a good resolution from captopril. In vitro interaction studies of captopril with commonly administered H2 receptor antagonists i.e. cimetidine, ranitidine and famotidine were carried out at 37°C using above validated method. These studies clearly indicated that H2-receptor antagonists bind to captopril causing drastic changes in the availability of the drug.

Synthesis and biological evaluations of enoxacin carboxamide derivatives

The present work deals with the synthesis of various enoxacin analogues via nucleophilic substitution of 3-carboxylic acid moiety of the drug by aromatic amines. The free carboxylic group was utilized in the formation of amides and the effect of functional group exchange on different biological activities of the parent was evaluated. The structure of these derivatives was established by various spectroscopic techniques and mass spectrometry. The derivatives were evaluated as antibacterial agents against a series of Gram-positive and Gram-negative bacteria whereby some of them displayed considerably improved antimicrobial profile against Gram-negative test strains. Additionally unlike enoxacin, the derivatives were also found to modulate oxidative burst response of phagocytes exhibiting moderate to significant inhibitory activity.

Monitoring of in vitro interaction studies of enalapril with hypoglycemic agents by LC-UV

The coadministration of antihypertensive and antidiabetic drugs is common, as both of these ailments are synergistic to each other and often occur together. In the present paper, we describe in vitro drug interactions of enalapril, an antihypertensive drug, with the hypoglycemic agents, metformin, glibenclamide, and glimepiride. These studies were carried out using an isocratic reversed phase high-performance liquid chromatographic method using a C18 column with ultraviolet detection at 230 nm. The system was operated at room temperature using a mobile phase consisting of methanol:water (70:30) adjusted to pH 2.5 with o-phosphoric acid with a flow rate of 1 mL minute −1 . The assay was reproducible, linear (concentration range of 2.5-100 µg mL −1 ) with a correlation coefficient of 0.9999 and an accuracy rate of 98%-102%. The results from the reversed phase high-performance liquid chromatographic method clearly indicated that the availability of enalapril was unaffected by the simultaneous administration of hypoglycemic agents. Hence, the two drugs can be safely administered with one another.

Development of a RP-HPLC method for the simultaneous analysis of diltiazem and statin: Application in pharmaceuticals and human serum

High-performance liquid chromatographic (HPLC) method has been developed and validated for the simultaneous determination of diltiazem and statins in raw materials, their pharmaceutical formulations and human serum. In HPLC, diltiazem and statins are chromatographed using acetonitrile–water (85:15 v/v, pH 2.6 ± 0.02) as the mobile phase at a flow rate of 1.0 mL min−1 at ambient temperature. The separation is carried out on a Hiber®, 250-4.6 RP-18 column, equipped with a UV/visible detector at 230 nm. All the statins eluted at a different retention time and each showed good resolution from diltiazem. The method has been successfully applied to pharmaceutical formulations because no chromatographic interferences from the tablet excipients are found. The linearity is found to be in the range 0.625–20 μg mL−1. The suitability of the method for the quantitative determination of the drugs is proven by validation in accordance with the requirements laid down by the International Conference on Harmonization (ICH) guidelines. The validation results, together with statistical treatment of the data, demonstrated the reliability of this method.

Spectrophotometric method for quantitative determination of montelukast in bulk, pharmaceutical formulations and human serum

A simple ultraviolet spectrophotometric method for the estimation of montelukast in methanol has been devised and been compared with the existing pharmacopoeial RP-HPLC method for estimation of the drug. The limit of detection of montelukast at 283 nm was 75.2 ng/mL. The calibration was linear in the range of 3–45 μg/mL. Analytical parameters such as stability, selectivity, accuracy and precision have been established for the method in MONAKA® tablets and in human serum and evaluated statistically to assess the application of the method. The method was validated under the ICH and USP guidelines and found to comprise the advantages for simplicity, stability, sensitivity, reproducibility and accuracy for using as an alternate to the existing non-spectrophotometric methods for the routine analysis of the drug in pharmaceutical formulations and in pharmaceutical investigations involving montelukast.

Determination of Tryptophan in Raw Materials, Rat Brain and Human Plasma by RP-HPLC Technique

This paper describes tryptophan (TRP) estimation in raw human plasma and rat brain by reversed-phase high-performance liquid chromatography (RP-HPLC). Estimation was carried out on a Purospher STAR C18 column using water-acetonitrile (90:10 v/v, at pH 2.7) mixture at a rate of 1.5 mL/min as mobile phase. Eluents were monitored at 273 nm by an ultraviolet detector. The method was linear (R(2) > 0.999), precise (intra-day and inter-day precision <2%) in the range of 0.25-20 µg/mL. The detection and quantification limits were 0.0144 µg/mL and 0.0437 µg/mL, respectively. In human plasma, Day 1 and Day 2 precision were 0.054-2.29% and 1.66-3.7%; whereas precisions in rat brain were 1.23-2.3% and 0.677-4.2%, respectively. The method was applied to study TRP level in human smokers and in arthritic rat brain. An efficient RP-HPLC method was developed for TRP determination that worked for clinical and research purposes.

IN VITRO STUDIES OF INTERACTION BETWEEN METFORMIN AND NSAIDS (NON STEROIDAL ANTI-INFLAMATORY DRUGS) USING SPECTROPHOTOMETRY AND RP-HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

Patients diagnosed with diabetes are prescribed a large number of medications for appropriate therapy, increasing risk of side effects or drug interactions. Metformin, a guanidine derivative is commonly used as a drug of choice for the treatment of non insulin dependent diabetes mellitus. There are a number of interactions reported for metformin. On the other hand, NSAIDs are generally used for the treatment of pain, fever and inflammation, particularly arthritis. Since the former drug is used in long term therapy, it may be co-administered with other drugs. In the present paper, we investigated the in-vitro availability of metformin in presence of commonly used NSAIDs, like diclofenic sodium, flurbiprofen, ibuprofen, mefenamic acid, meloxicam and tiaprofenic acid. These studies were carried out using modified BP 2007 dissolution test apparatus in simulated body environments at 37oC. These drug interactions were analyzed by UV/ VIS spectroscopy and the effect on the availability of both metformin and NSAIDs in presence of each other was calculated by applying simultaneous equation which was derived by modifying Beers law. The interactions were further studied by RP-HPLC with mobile phase consisting of methanol and water (80:20 v/v) maintained at a flow rate of 1 mLmin -1 at isobestic point 241 nm (metformin, diclofenac sodium, flurbiprofen, tiaprofenic acid, ibuprofen, meloxicam and mefenamic acid) respectively. The results showed that the in vitro availability of NSAIDs and metformin owing to interaction was depressed through the formation of charge transfer complexes which was found to be associated with inter- and intra-molecular rearrangement of the electronic cloud of the interacting drugs. Hence it is envisaged that concurrent administration of metformin and NSAIDs could alter the bio-availability and impair the clinical efficacy of both drugs. Effect of pH is also studied on these drug-drug interactions.