Development and Validation of a RP-Ultra performance liquid chromatographic Method for Quantification of Topotecan Hydrochloride in Bulk and Injection Dosage Form.

A simple, very fast, precise and accurate reverse phase ultra performance liquid chromatographic method was developed for the determination and validation of topotecan hydrochloride in bulk and injection dosage form. A Waters BEH C18, 50×2.1 mm, 1.7 µm particle size column in gradient mode was used with mobile phase comprising of 0.1% v/v orthophosphoric acid in water and acetonitrile. The analytical column was thermostated at 50° and flow rate was set at 0.4 ml per min, with photo diode array detection at 260 nm. The retention time of topotecan was found 1.38 min. The method was validated in terms of linearity, accuracy, precision and specificity. The calibration curve was found linear between 20 to 60 µg/ml. The limit of detection and limit of quantification were found 0.2353 and 0.7131 µg/ml, respectively. Percentage recoveries were obtained in the range of 98.91% and 99.17%. The proposed method is precise, accurate, selective and reproducible. The ultra performance liquid chromatographic assay procedure, which proved superior because of its greater sensitivity and relatively shorter (4 min) run time, should be an important tool for speedy future analysis of topotecan hydrochloride in bulk and its injection dosage form.

Effect of high altitude (7,620 m) exposure on glutathione and related metabolism in rats.

Reduced and oxidised glutathione (GSH and GSSG) contents, and glutathione reductase, and glutathione S-transferase activities were studied in the livers, muscles, and blood/erythrocytes of male Sprague-Dawley rats exposed to intermittent hypoxia (6 h.day-1) at a simulated altitude of 7,620 m for 1, 7, 14, and 21 days. Significant decreases in GSH and increases in GSSG contents were observed in the muscles and blood of hypoxia-exposed rats in comparison to unexposed rats. Significant declines in GSH content by 43% and 45% respectively in muscles and blood were observed in the group exposed for 1 day which tended to recover on subsequent exposure. Glutathione reductase and glutathione S-transferase activities were decreased in the livers and erythrocytes of hypoxia-exposed rats, but were increased significantly in muscle. Lipid peroxidation was also increased in the livers and muscles of exposed rats. The changes were indicative of an increased production of reactive oxygen species and an impairment of drug and xenobiotic metabolism during exposure to high altitude hypoxia.

Effect of hypoxia on the circulating levels of essential mineral elements in rats.

Changes occurring in concentrations of certain trace metals and electrolytes viz. chromium, copper, zinc, sodium, potassium, calcium, magenesium and chloride in plasma of rats exposed to intermittent hypobaric hypoxia were evaluated. Batches of Sprague-Dowley rats (12 in each group) were exposed for 1, 7,14 and 21 days to a simulated altitude 7,620 m for 6 h per day and one group of unexposed animals was kept as control. There was a significant rise of 153% in plasma chromium levels of 1 day exposed group in comparison to the unexposed group which tends to normalise on subsequent exposure. There was a gradual increase in plasma copper levels of 9.0, 28.2, 62.6 and 65.6% respectively in 1,7,14 and 21 days exposed rats in comparison to unexposed rats. On the other hand plasma zinc levels were seen to be decreasing during entire exposure. Plasma sodium levels decreased initially in 1 and 7 day exposed rats and increased in later groups whereas plasma potassium levels of exposed groups remained low in comparison to unexposed group. Chloride levels were found to be elevated in 14 and 21 day exposed groups. The plasma calcium and magnesium levels were higher in all exposed groups over unexposed groups. Changes in chromium, copper and zinc observed in the present study during exposure to hypoxic stress may be responsible for the hyperglycemia and anorexia encountered during intial phase of high altitude acclimatisation.

A community-based study on the effect of hexachlorocyclo-hexane (HCH) exposure in spraymen and general population.

The study was carried out in Allahabad district, (Uttar Pradesh) with 260 spraymen as test subjects and 50 persons as controls from a sprayed and unsprayed village respectively. Majority of the spraymen (44%) had worked for 3-4 years (seasons) and 31% had worked in the programme for 5-10 years. The spraymen were relatively healthy with no complaints in 77% whereas the figures were 76% for the Community living in the sprayed village, and 50% for the Community in the unsprayed village. A comparison of the biochemical parameters revealed lowered Cholesterol more than 150 mg % in 38% of the spraymen and 58% had altered A:G ratio. Other biochemical estimations were not significantly different from the control population. The mean residue of Alpha, Beta and Gamma Isomers and the total Alpha, Beta and Gamma isomers were 0.0317, 0.2254, 0.0288 and 0.2859 mg/1 respectively; the corresponding mean values in the control population were 0.0211, 0.1112, 0.0197 and 0.1520 mg/1 respectively. The values in spraymen were twice those of the general population. A significant association (p < .05) was observed between their length of exposure and the levels of Cholesterol and HCH isomers in blood of spraymen. No significant morbidity was evident in spraymen due to HCH exposure.

Simultaneous determination of chlorzoxazone and acetaminophen in combined dosage forms by an absorbance ratio technique and difference spectrophotometry.

Two spectrophotometric methods have been developed for the simultaneous determination of chlorzoxazone and acetaminophen in their combined dosage forms. No preliminary separation step is required in either method. The first, an absorbance ratio technique using the isoabsorptive point as one of the wavelengths, together with "Q curve" analysis gives accurate and reproducible results for both drugs. The second, a difference spectrophotometric method is based on measurement of absorbance of an alkaline solution relative to that of an acidic solution of identical concentration of the sample at two different wavelengths. The method is suitable for routine analysis of such combinations of the drugs.

Spectrophotometric assays of diloxanide furoate and tinidazole in combined dosage forms.

Two spectrophotometric methods have been developed for the simultaneous determination of diloxanide furoate and tinidazole in combined dosage formulations without prior separation. The first method is based on the measurement of the absorbance of a methanolic solution of the sample at 259 and 311 nm and application of a simplified Vierordt equation for the determination of diloxanide furoate, whereas tinidazole is determined by direct spectrophotometry. The second method is a difference spectrophotometric procedure based on measurement of the absorbance of the sample solution in water relative to that of an acidic or alkaline solution of identical concentration at the appropriate wavelength of maximum difference absorption. The results are calculated by reference to standard absorptivity values.