Quantitation of Testosterone,Cypionate-in-Oil Injection Using High-Performance Liquid Chromatography.

A high-performance liquid chromatography assay method for the quantitation of testosterone-cypionate-in-oil injection has been developed. The assay method is very simple, accurate and precise, with a percent relative standard deviation of 1.2 based on five readings. The extraction procedure is very simple compared with a very tedious and time-consuming procedure given in the United States Pharmacopoeia/National Formulary. The USP-NF assay method is based on gas chromatography. The benzyl alcohol (preservative) did not interfere with the assay preocedure. The newly developed method could not be applied to the quantitation of testosterone enanthate since the results were consistently low (-87%). The average recovery of testosterone cypionate from a commercial dosage form was 98.7%.

Stability of Lorazepam in 5% dextrose injection.

The adsorption of lorazepam in intravenous admixtures onto 50-mL polyvinyl chloride (PVC) bags has been studied using a spectorphotometric assay method reported in the literature. This method indicated a loss of 7.7% to 9.5% versus a high-performance liquid chromatography (HPLC) assay method developed in our laboratory, which showed a loss of 4.9% to 5.5%. In the spectrophotometric assay method, benzyl alcohol (the preservative in the lorazepam injection) interfered with the assay procedure. The HPLC assay method separated the peak of lorazepam from the benzyl alcohol peak. It also showed that part of the loss as determined by spectrophotometric assay method was due to the absorption of benzyl alcohol. The adsorbed lorazepam was adsorbed in less than six hours and there was no more loss after that. By storing different volumes of the admixture (20, 30, 40, and 50 mL) vertically in 50-mL PVC bags, the loss of drug due to adsorption did not show any siginificant differences.

Chemical stability of amiodarone hydrochloride in intravenous fluids.

The chemical stability of amiodarone hydrochloride in two intravenous (IV) fluids, 5% dextrose injection and 0.9% sodium chloride injection, was studied. Drug degradation was monitored using a stabiility-indicating, high-performance liquid chromatography assay method. The admixtures of amiodarone in the two IV fluids were found to be stable for 32 days when refrigerated (5 deg C) , and also at room temperature (25 deg C). All solutions remained clear during this period. The recommendations from the manufacturer are conservative. The admixtures are apparently physically and chemically stable for more than 24 hours, provided they are protected from microbiological contamination. However at 40 deg C, significant degradation was observed ater 18 days; and the solutions turned cloudy. Precautions must be taken to prevent temperature elevation during storage.

Assessment of potential health risks associated with ingesting heavy metals in fish collected from a hazardous-waste contaminated wetland in Louisiana, USA.

Significant adverse effects on environmental quality, ecosystem integrity, and human health have often been associated with improper disposal of hazardous materials. This study ascertains the levels of eight heavy metals in various fish species that were collected from a local hazardous-waste-contaminated wet-land and estimates the potential health risk that may be associated with consuming such fish. We examined a total of 53 fish samples representing 12 different species. The respective mean concentrations (ng/g) of arsenic, cadmium, chromium, copper, iron, lead, mercury, and nickel found in edible tissues were as follows: 72.5 +/- 103.1, 55.4 +/- 34.6, 97.4 +/- 111.7, 177.3 +/- 328.3, 2711.0 +/- 4469.6, 26.0 +/- 119.0, 32.7 +/- 75.3, and 81.5 +/- 178.9. For a 10-kg child eating 6.5 g of fish per day, the computed combined hazard index was 0.475 ; for 70-kg adults with a daily consumption of 6.5 g (general population), 30 g (sport fishermen), and 140 g (subsistence fishermen), the respective computed hazard indices were 0.068, 0.313, and 1.462. The results indicate that subsistence fishermen had the highest risk for systemic effects, with an exposure exceeding the Environmental Protection Agency (EPA) Reference Dose value. In a 10-kg child, such excess exposure would be reached--even with such single metals as arsenic and mercury--when applying the EPA-approved maximum fish consumption rate of 54 g/day to the general population. The cancer risk for arsenic, the only metal with an established cancer potency factor from oral exposure, varied from 8 x 10(-6) to 253 x 10(-6), indicating an exposure exceeding the widely accepted risk level of 1 x 10(-6) (one excess cancer per 10(6) population).

Chemical stability and adsorption of atracurium besylate injections in disposable plastic syringes.

Atracurium besylate (AB) is supplied as a sterile, non-pyrogenic aqueous solution for intravenous use. Hospitals pre-fill disposable plastic syringes with these solutions so that they are ready for immediate use when required. Drug loss due to potential adsorption on to the plastic material of the syringes has not been studied. Atracurium is also administered by intravenous infusion using a diluted solution in either 5% dextrose injection (USP) or 0.9% sodium chloride injection USP. Drug solutions not used within 24 h are usually discarded, resulting in tremendous waste. The purpose of these investigations was to determine the adsorption behaviour of atracurium when stored in plastic syringes, and to study the degradation of atracurium in i.v. fluids. For the adsorption study, 10 mg/ml solutions were used, whereas the diluted infusion solutions were prepared to contain 0.5 mg/ml of atracurium. Drug degradation was monitored using a stability-indicating high-performance liquid chromatography method. Degradation studies were conducted at 5 degrees C, 25 degrees C and 40 degrees C. Refrigeration was observed to improve drug stability. The manufacturer's recommended expiry period was too conservative. Storage at room temperature for up to 6 weeks can be safely recommended, without significant loss of chemical stability.

Chemical stability and adsorption of succinylcholine chloride injections in disposable plastic syringes.

The purpose of these investigations was to determine the stability and adsorption behaviour of succinylcholine chloride (SCC) when stored in plastic syringes. Drug degradation was monitored using the USP high-pressure liquid chromatography method. Solutions containing 20 mg/ml of SCC in 5% dextrose, and in normal saline, were studied at 5, 25 and 40 degrees C. The hydrolysis of SCC in i.v. fluids followed apparent zero-order kinetics. The manufacturer's recommended expiry period was found to be too conservative. If protected from light, storage at room temperature for up to 3 months can be safely recommended, without significant loss of chemical stability. However, microbiological quality assurance will need to be implemented and an appropriate shelf-life assigned on the basis of both microbiological and chemical stability data.

Development of a stable oral liquid dosage form of spironolactone.

A clear, stable, oral liquid dosage form of spironolactone has been developed. Solubility profiles of spironolactone were obtained in several co-solvent blends. Using this data, a co-solvent blend containing polyethylene glycol 400 (30% v/v), propylene glycol (10% v/v), glycerin (10% v/v) and ethyl alcohol (10% v/v) was used to solubilize spironolactone at a concentration of 2 mg/ml. The final formulation contained sweetening agents (sucrose, saccharin sodium), flavours (cherry, sweet), a desensitizing agent (menthol), a dye (FD&C Red #40) and a preservative (benzoic acid) to incorporate the desired organoleptic and preservative properties. A phosphate buffer was used to maintain a pH value of 4.5 (pH of maximum stability as reported earlier) to minimize hydrolysis. The final dosage form was stable for at least 93 days at 40 degrees C (loss of potency less than 4%). According to FDA guidelines, a tentative expiration date of 2 years at 25 degrees C is justifiable.

Stability of captopril in some aqueous systems.

A stability-indicating high performance liquid chromatographic method has been proposed to quantify captopril. The method has been used to determine the stability of captopril in oral liquid dosage forms prepared from either commercially available tablets or powder. The dosage forms in water were more stable than when the vehicle was a syrup. Furthermore, the dosage form prepared using powder in water was more stable than when tablets were used. While the decomposition of captopril followed first-order equation when the dosage forms were prepared in syrup (in two of the three solutions studied), this equation was not followed when water was the vehicle. This is probably due to an uncontrolled factor, oxygen, because captopril is very sensitive to oxidation. Captopril solution prepared in water using tablets was stable for about 20 days when stored at 5 degrees C, and that prepared using powder in water was stable for about 27 days. One commercial syrup hastened the process of decomposition with an additional unidentified product of decomposition.

Stability of cefuroxime axetil in suspensions.

Cefuroxime axetil is a mixture of two equally active isomers (50% each). A stability-indicating high-pressure liquid chromatography method for the quantification of cefuroxime axetil has been developed. The method is accurate, precise and reproducible. The percentage, relative standard deviation based on six injections was 1.2. Using the developed method, the chemical stability of cefuroxime axetil suspensions has been determined in three vehicles containing sugar and two without sugar. The results varied widely in the vehicles without sugar (up to +/- 31%). In the viscous vehicles containing sugar, the variations in the results were only up to +/- 6%. The cefuroxime axetil in these suspensions was stable up to 28 days when stored at 5 degrees C. In addition, pH values were stable and the physical appearances of the samples did not change.

Stabilities of dobutamine, dopamine, nitroglycerin and sodium nitroprusside in disposable plastic syringes.

The solutions of dobutamine hydrochloride (5 mg/ml), dopamine hydrochloride (4 mg/ml), nitroglycerin (1 mg/ml) and sodium nitroprusside (1 mg/ml) in dextrose 5% injection were stable for 24 h when stored at 25 degrees C in 60-ml plastic syringes. For sodium nitroprusside, the syringes must be wrapped with aluminium foil (provided by the manufacturer), otherwise the loss in potency is very high (22%). There was no change in the pH values of dobutamine and dopamine solutions as well as sodium nitroprusside solutions in the prewrapped syringes. However, the pH value of nitroglycerin solutions decreased to 4.3 from 4.6 and that of sodium nitroprusside solutions in unwrapped syringes from 4.2 to 3.5; these solutions had discoloured. The chromatogram also showed new peaks from the products of decomposition. The physical appearances of the other solutions did not change.

Preformulation studies of spironolactone: effect of pH, two buffer species, ionic strength, and temperature on stability.

Using a stability-indicating HPLC assay method, the effect of pH, two buffer species (citrate and phosphate), ionic strength, and temperature on the stability of spironolactone in 20% solution of ethyl alcohol in water has been studied. The optimum pH of stability appears to be approximately 4.5. On increasing the buffer concentration, both species hastened the decomposition of spironolactone. The ionic strength did not affect the stability of the drug. The energy of activation has been estimated to be approximately 78.8 kJ/mol at pH 4.3. The un-ionized spironolactone is subject to general acid-base catalysis. The Kh and Koh values at 40 degrees C have been estimated to be 1.63 and 2.8 x 10(5) day-1, respectively. The HPO4(-2) ion had approximately 10 times more catalytic effect than the H2PO4(-1) ion. This data will be used to develop a stable oral liquid dosage form of the drug.

Chemical stability of cefotetan disodium in 5% dextrose and 0.9% sodium chloride injections.

The chemical stability of cefotetan disodium in 5% dextrose and 0.9% sodium chloride injections has been studied using a stability-indicating high-pressure liquid chromatographic (HPLC) assay method. The drug appears to be relatively unstable at 25 degrees C (expiry time 2 days), compared with at least 41 days at 5 degrees C and at least 60 days at -10 degrees C. Thawing the frozen samples in a microwave (90 s) did not cause any significant decomposition. The manufacturer's recommended expiry time of 4 days at 5 degrees C and at least 7 days at -10 degrees C is very conservative. The HPLC method developed is accurate and precise with a relative percentage standard deviation of 1.7 based on six readings. The method appears to be stability-indicating as the samples decomposed under drastic conditions had almost no drug left and new peaks were observed in the chromatograms.

Stability of acyclovir sodium in dextrose and sodium chloride injections.

The chemical stability of acyclovir sodium in dextrose 5% w/v and sodium chloride 0.9% w/v injections has been studied using a stability-indicating high-pressure liquid chromatographic (HPLC) method. The drug appears to be very stable in both admixtures. There was no decomposition after 37 days of storage at 25 degrees C or 5 degrees C. The manufacturer-recommended expiry date of 24 h at 25 degrees C is too conservative. The solutions were clear throughout the study period and the pH values had decreased slightly in both the solutions. Acyclovir appears to be very stable on the alkaline side of the pH range and less so on the acidic side. There was no loss in the potency of acyclovir when mixed with dobutamine and dopamine.