Harish Padh

A new liquid-liquid extraction method for determination of montelukast in small volume human plasma samples using HPLC with fluorescence detector

Montelukast is a potent orally active cysteinyl leukotriene receptor antagonist that significantly improves parameters of asthmatics. A new liquid-liquid extraction based reverse phase liquid chromatography method has been developed and subsequently validated for the determination of montelukast in human plasma. The separation was achieved with C8 column (150×4.6 mm, 5 micron) and a mobile phase comprising of a mixture of 10 mM ammonium acetate buffer (pH 3.0) and acetonitrile in a ratio of 35:65 v/v. Montelukast was extracted from human plasma using a liquid-liquid extraction technique with ter-butylmethylether. The limit of detection and lowest limit of quantification were 5 and 10 ng/ml respectively. This method was found to be linear over the range of 10 to 1000 ng/ml with a recovery of 53 to 62%. Intraday and interday precision (% CV) was <15% and accuracy ranged from 96.23 to 108.39%. Stability studies showed that montelukast in human plasma is stable during the short-term period of sample preparation and analysis. This method can be used with small volume sample during pharmacokinetic studies.

Pharmacokinetic profile of a new formulation of injection diclofenac designed for intradeltoid use.

Objective: Injection diclofenac sodium available at present as a 3-ml formulation is administered intragluteally. Standard needles may not reach the gluteus maximus muscle in many cases, especially in obese patients. Alternative sites like the deltoid have been suggested to be more suitable for these patients. Diclofenac sodium 75 mg/ml was prepared to facilitate intradeltoid adminis-tration. The objective of this study was to determine pharmacokinetic parameters and to compare the bioavailability of the new formulation of injection diclofenac sodium (75 mg/ml), given as an intradeltoid injection, with the reference formulation (75mg/3 ml) given intragluteally. Research design/methods: A single-dose, two-way bioequivalence study was carried out in 18 healthy, Indian, male volunteers with a washout period of 5 days. Blood samples were collected up to 6 h after drug administration and analyzed using a prevalidated HPLC method. Results: The mean Cmax and Tmax, for the test and reference formulations were 1.95 μg/ml, 1.89 μg/ml and 0.39 h, 0.43 h respectively. AUC values from 0 to last measurable time point ‘t’ observed for test and reference formulations were 3.37 μg.h/ml and 3.28 μg.h/ml respectively. The mean AUC 0 – infinity for test and reference formulations was 3.57 μg.h/ml and 3.52 μg.h/ml. Conclusion: Results suggest that the test and reference formulations of injection diclofenac sodium 75 mg given intradeltoid and intragluteally are bioequivalent. The test formulation would be especially helpful in the management of obese/overweight patients and patients with thick subcutaneous fat in the gluteal region. It would increase the success rate of intramuscular deposition of the medication.

Pharmacogenetics: Genetic basis for rational drug therapy

Pharmacogenetics has revolutionized the way in which drug metabolism was looked upon in the pre-genomic era. Today with the advent of genomics it is possible to genotype an individual. The genetic differences, which determine the disposition of a given drug in an individual, ultimately give differences in drug response. Genotyping and phenotyping tests to predict dose requirement are now increasingly introduced during preclinical and clinical studies of new drugs. However, the hypothesis for the genotype and the phenotype correlation has to be established. Once this correlation will be established and technology to genotype advances enough to give predictive values over 90%, pharmacogenetics will enter the clinics. Pharmacogenetics will help to tailor the drug type and its dosage according to the individuals genotype. It will help to minimize adverse drug reactions as well as cases of non-responders to the drug therapy. In addition, this will provide better understanding of pharmacogenetic variations both within as well as among major populations/groups of the world.