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A stability-indicating high performance liquid chromatography assay method was developed to quantify metroprolol tartrate in pharmaceutical dosage forms. The method can also be used to quantify propranolol hydrochloride in injections and tablets. It is precise and accurate with a percent relative standard deviation of 0.9% for metoprolol and 0.7% for propranolol based on five determinations. The use of a counterion in the mobile phase is not required as described in the USP-NF method. Also, the procedure for extracting the drugs from tablets is very simple and does not require mechanical shaking for 30 minutes as described in the USP-NF. The new method was used to study the stability of metoprolol in an aqueous mixture. The drug was stable for at least 10 days when stored at 25 deg C in amber-colored bottles. However, 10% of the drug was not available due to adsorption onto the excipient. Solutions to this problem have been recommended.

The stability of cefmetazole sodium in 5% dextrose injection and 0.9% sodium choloride injection has been studied using a stability-indicating, high performance liquid chromatography (HPLC) assay method developed in our laboratory. This HPLC method is precise and accurate, with a percent relative standard deviation of 1.4 based on five readings. The admixtures were stable for two days at 25 deg C and for 28 days at 5 deg C, and they remained clear throughout the study period. The pH values decreased from 4.7 to 4.0 in 0.9% sodium chloride injection and from 4.8 to 4.2 in 5% dextrose injection. The expiry date of seven days at 5 deg C recommended by the manufacturer appears to be conservative from a chemical-stability standpoint.

The stability of indomethacin (from indomethacin sodium trihydrate powder for injection) in preservative-free 0.9% sodium chloride injection has been studied using a stability-indicating high-performance liquid chromatography assay method. The method described is precise and accurate, with a percent relative standard deviation of 0.7% based on five readings. The 0.1-mg/mL solutions were stable for at least ten days when stored at roomtemperature in 10-mL plastic vials in which the sodium chloride injections are marketed. The solutions remained clear throughout the study;and pH values did increase by about 0.5 units, since the admixtures were not buffered.

The stability of cefepime hydrochloride in 5% dextrose injection and 0.9% sodium chloride injection was studied using a stability-indicating assay method developed in our laboratory. This method is precise and accurate, with a percent relative standard deviation of 0.7% based on five readings. The admixtures were stable for two days at 25 deg C and 23 days at 5 deg C. The pH values of the admixtures did not change throughout this study, and the colors had changed from a very light yellow to a light yellow. The manufacturer recommends an expiry date of 24 hours at 20 to 25 deg C and seven days at 2 to 8 deg C.

The chemical stability of bethanechol aqueous solutions prepared using either tablets, injection or powder was studied. For an aqueous solution prepared using tablets, the initial result was low (86.5%) and the pH value was 7.1. With storage at 25 deg C, the result increased to almost 100% in 12 days and the pH value decreased to about 3.4. For the solution prepared from the injection, the initial result was 100%. After 40 days' storage at 25*C, the pH value decreased from 7.0 to 6.0 and the result was still almost 100% of the label claim. The aqueous solutions prepared from powder in phosphate buffers (pH values between 3.0 and 6.8) retained almost 100% of the potency at all pH values.

The chemical stabilities of ceftriaxone sodium and metronidazole in a mixture have been studied using a stability-indicating, high-performance liquid chromatography (HPLC) assay method. The HPLC method is precise and accurate, with a percent relative standard deviation of 1.4 based on five readings. Metronidazole did not lose any potency for four days when stored at 25+/-1 deg C. Ceftriaxone sodium lost less than 6% ofpotency in three days at 25+/-1 deg C. The products of decomposition did not interfere with the assay procedure. They eluted before the ceftriaxone peak. The solution remained clear (light yellow) throughout the study period, and the pH value did not change. Ceftriaxone sodium and metronidazole, when mixed together, were stable for three days at 25+/-1 deg C.

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.

The stability of ketorolac tromethamine in 5% dextrose injection and 0.9% sodium cholride injection has been studied using a stability-indicating, high-performance liquid chromatography assay method developed in our laboratory. This method is precise and accurate, with a percent relative standard deviation of 0.85% based on five readings. The admixtures were stable for at least 50 days when stored at 5 deg C. At 25 deg C the 0.9% sodium chloride admixture was stable for at least 35 days, and in 5% dextrose injection for only seven days. After 14 days of storage at 25 deg C the pH value of the admixture in 5% dextrose injection had decreased from 6.6 to 4.3. The changes in pH values of all other admixtures were less than 0.55. This assay method can be used to quantify ketorolac tromethamine in injections and tablets.

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%.

A high-performance liquid chromatographic assay method for the quantitation of alatrofloxacin in intravenous (IV) admixtures has been developed. The method is accurate and precise, with a percent relative standard deviation of 1.2% based on five injections. The method is stability indicating since the product of decomposition, trovafloxacin, did not interfere with the assay procedure. The IV admixtures of alatrofloxacin (1.88 mg/mL) in 5% dextrose and 0.45% sodium-chloride injections were stable for at least nine days when stored at room themperature. The pH values of the admixtures did not change and they remained clear throughout this study.

A high-performance liquid chromatography assay method for the quantition of testosterone propionate in an injection has been developed. The assay method is very simple, precise and accurate, with a percent relative standard deviation of 1.3 based on five injections. The benzyl alcohol (the preservative) and sesame oil (the vehicle) did not interfere with the assay procedure. The extraction procedure is very simple compared with a tedious and time-consuming method recommended in the USP-NF. The other similar compounds, testosterone, methyltestosterone, testosterone cypionate and testosterone enanthate, did not interfere with the assay method. Hence, the method developed is specific for this drug, versus the USP-NF method, which is nonspecific.

A high-performance liquid chromatographic assay method for the quantitation of trovafloxacin in film-coated tablets and an oral liquid dosage form (10 mg/mL) prepared from tablets has been developed. The assay method is very simple, precise and accurate, with a percent relative standard deviation of 1.8 based on five injections. The recovery from the tablets and the oral liquid dosage form was very close to the label claims. The method is stablilty indicating, since the peak from a degraded sample (using sodium hydroxide) did not interfere with the assay procedure. Furthermore, a number of excipients present in the tablets and the oral liquid dosage form did not interfere with the developed method. The oral liquid dosage form gave uniform results and the drug was stable for at least 14 days when stored in an amber-colored glass bottle at 25 deg C(+/-1). The pH of the formulation did not change.

An assay method based on high-performance liquid chromatography (HPLC), for the quantitation of testosterone in an aqueous suspension, has been developed. The method is very simple compared with a tedious and time-consuming method recommended by the USP-NF. It is an accurate and precise method; the percent relative standard deviation based on five injections was 1.15. The average recovery from four batches of suspension was 100% (percent relative standard deviation, 1.3) A number of inactive ingredients present in the suspension vehicle did not interfere with the assay procedure. Testosterone appears to be a very stable drug since it did not decompose significantly, even on heating. A 15-cm column gave sharper peaks vs. a 25-cm column and the sensitivity of the assay method increased by 400%.

The stability of acyclovir sodium (10 mg/mL) in 0.9% sodium chloride injection has been studied at 25 deg C and 5 deg C in polypropylene syringes by means of a stability-indicating high-performance liquid chromatography (HPLC) assay method. The concentrations of the drug were directly related to peak heights, and the percent relative standard deviation (RSD) based on 5 injections was 1.0. At 25 deg C, there was no loss in potency after 30 days of storage, and at 5 deg C, the drug had begun to precipitate within 5 days. Therefore, the stability could not be investigated. The pH values of the injections were between 10.4 and 10.7. The drug was not adsorbed onto the syringes, and the physical appearance of the injection did not change.

The stability of ethacrynate sodium (1 mg/mL) in 0.9% sodium chloride injection has been studied at 25 deg C and 5 deg C in polypropylene syringes by using a stability-indicating high-performance liquid chromatography assay method. The concentrations of the drug were directly related to peak heights, and the percent relative standard deviation based on 5 injections was 1.6. Mannitol, which is added as an excipient in the injection, did not interfere with the assay procedure. Two products of decomposition separated from the intact drug. At 25 deg C, there was no loss in potency after 14 days of storage or at 5 deg C after 22 days of storage. the pH value (6.5) of the injection remained constant throughout the study period. The drug was not adsorbed onto the syringes and the physical appearance of the injection did not change.

The stability of pentobarbital sodium (10 mg/mL) in 0.9% sodium chloride injection and pentobarbital sodium (50 mg/mL) after repackaging in glass and polypropylene syringes has been studied at 25 deg C by means of a stability-indicating high-performance liquid chromatography assay method. The concentrations of the drug were directly related to peak heights, and the percent relative standard deviation based on 5 injections was 1.7. The pH value of the sample, which was prepared by diluting the injection (50 mg/mL) to 10 mg/mL with 0.9% sodium chloride injection, decreased from 9.2 to 8.2. At this pH, the free base began to crystallize out in less than 24 hours. After the undiluted commercial injection was repackaged in glass or polypropylene syringes, there was no significant loss of potency after 31 days of storage at 25 deg C. The pH value of the injection remained constant at 9.2.The pentobarbital sodium in injection appears to be very stable, because the loss in potency was only about 6.2% after it was boiled in water for 1.5 hours.

The chemical stability of methylprednisolone sodium succinate (10 mg/mL) in 0.9% sodium chloride injection has been studied at 25 deg C and 5 deg C in polypropylene syringes by means of a stability-indicating high-performance liquid chromatography assay method. The concentrations of the drug were directly related to the peak height, and the percent relative standard deviation based on five injections was 1.2. Benzyl alcohol, which is added as a preservative, did not interfere with the assay. Two products of decomposition separated from the intact drug. At 25 deg C, the loss of potency was less than 10% after 4 days of storage. At 5 deg C, the loss of potency was less than 5% when the injection was stored for 21 days. After 17 days of storage at 25 deg C, the pH value of the injection decreased from 7.2 to 6.5, and there was no change in the pH value when the injection was stored for 21 days at 5 deg C. The drug did not adsorb onto the syringes, and the physical appearance of the injection did not change.

The stability of ethacrynic acid (2.5 mg/mL) in oral liquid dosage forms was investigated. Tablets in 0.05 M phosphate buffer (available commercially) in water were used to prepare the dosage forms. The effects of mannitol and sugar on the stability of ethacrynic acid were negligible. There was no change in the physical appearance of the oral liquid dosage forms or pH values during the study. There was, however, a new peak in the chromatogram from the products(s) of decomposition. An oral liquid dosage form of ethacrynic acid containing 0.05 M phosphate buffer and 10% mannitol was stable for 24 days when stored at 5 deg C and for only 3 days when stored at 25 deg C.

The stability of nafcillin sodium (10 mg/mL) in 0.9% sodium chloride injection has been studied at 25 deg C and 5 deg C in polypropylene syringes by means of a stablilty-indicating high-performance liquid chromatograph assay method. The concentrations of the drug were directly related to peak heights and the percent relative standard deviation based on 5 injections was 1.2. The sodium citrate (added as a buffering agent in the powder) did not interfere with the assay procedure. The product(s) of decomposition separated from the intact drug. At 25 deg C, the loss in potency was less than 2% after 7 days of storage, and at 5 deg C it was also less than 2% when stored for 44 days. The pH values of the injections were between 6.2 to 7.0 throughout this study, except after 14 days of storage at room temperature (potency, 82.3%; pH,5.3). The drug did not adsorb to the syringes, and the physical appearance of the injection did not change. Nafcillin sodium was considered stable for at least 7 days at 25 deg C and 44 days at 5 deg C.

A stability-indicating assay method has been developed to quantify glycopyrrolate in an oral liquid dosage form. The developed method is accurate and precise and has a percent relative standard deviation of 1.8 based on 5 injections. The deomposition product and the excipients present in the dosage form did not interfere with the assay procedure. An oral liquid dosage form (0.5 mg/mL in water) that was prepared using 1-mg commercially available tablets was stable for 25 days (loss in potency, 8.2%). During that time, the pH value of the dosage form decreased from 6.8 to 6.6.

The stabilty of hydrocortisone sodium succinate (10 mg/mL) in 0.9% sodium chloride injection has been studied at 25 deg C and 5 deg C in polypropylene syringes by means of a stabililty-indicating high-performance liquid chromatography assay method. The concentration of the drug was directly related to the peak height, and the percent relative standard deviation based on 5 injections was 1.2. Benzyl alcohol, which was added as a preservative, did not interfere with the assay procedure. Two products of decomposition separated from the intact drug. At 25 deg C, the loss in potency was less than 10% after 7 days of storage. At 5 deg C, it was less than 3% when stored for 21 days. The pH value of the injection decreased from 7.2 to 6.3 when stored at 25 deg C for 21 days and from 7.2 to 7.0 when stored at 5 deg C for 21 days. The drug did not adsorb onto the syringes, and the physical appearance of the injection did not change.

A stability-indicating high-performance liquid chromatography (HPLC) assay method was used to study the stability of piperacillin sodium (40 mg/mL) in 0.9% sodium chloride injection at 25 deg C and 5 deg C in polypropylene syringes. The concentrations of the drug were directly related to peak heights, and the percent relative standard deviation (RSD) based on five injections was 0.8. Three products of decomposition separated from the intact drug. At 25 deg C, the loss in potency was less than 10% after 5 days of storage, and at 5 deg C, it was less than 2% when stored for 28 days. The pH value of the injection decreassed from 5.3 to 4.4 when stored for 28 days at 5 deg C. The drug was not adsorbed onto the syringes, and the physical appearance of the injection did not change.