Contamination of injectable solutions with 2-mercaptobenzothiazole leached from rubber closures.

An impurity, discovered in a sample of digoxin injectable solution commercially packaged in a syringe for single-dose delivery, was found to originate from the rubber closure of the syringe and was identified as 2-mercaptobenzothiazole, a common accelerator for rubber vulcanization. Several similarly packaged injectable solutions of a variety of drugs from various manufacturers were examined and over half contained 2-mercaptobenzothiazole. The compound was identified by UV spectrophotometry (including a pH-dependent shift in its absorbance maximum), by mass spectrometry, and by comparison with standard 2-mercaptobenzothiazole using silica gel and reverse-phase high-performance liquid chromatography (HPLC). The presence of this impurity in injectable solutions may have implications with regard to toxicity and may interfere with the assay of digoxin injectable solution by HPLC.

Stability of prednisone tablets submitted by U.S. hospitals.

The stability of prednisone tablets that had been stored in hospitals across the United States was studied. Through a voluntary FDA drug stability program, all hospital pharmacies in the United States were asked in October 1982 to complete a response card indicating information about prednisone tablets they had in stock. Based on the responses, FDA selected 117 samples (representing 18 manufacturers and all available tablet strengths) from pharmacies that represented an adequate cross section of the country. The samples were analyzed for content uniformity, strength, identification, dissolution, and the presence of other steroids. All samples met USP requirements for content uniformity and strength. Four samples failed to meet USP requirements for dissolution. Prednisone tablets appear to be stable when stored under actual marketplace conditions.

Semiautomated method for analysis of nitroglycerin in sublingual tablets: collaborative study.

This method is a semiautomated version of the current USP XX method for content uniformity testing of nitroglycerin tablets. Nitroglycerin is hydrolyzed to nitrite in aqueous alkali. The nitrite thus formed diazotizes procaine, which then is coupled with Bratton-Marshall reagent; the absorbance of the resultant color is read at 550 nm. Six collaborators were supplied with 6 composites of sublingual tablets, representing 3 different dosage levels. Results agreed with those obtained by the author using the USP composite assay method. The coefficients of variation ranged from 0.20 to 0.70%. The method is sensitive enough for individual tablet assays (0.15 mg nitroglycerin). The method has been adopted as official first action.

A simple, inexpensive thin-layer chromatography method for the analysis of theophylline tablets.

A simple, low-cost thin-layer chromatography (TLC) procedure to estimate the quality of simple pharmaceuticals in tablet form is described together with easily built equipment to carry out the test in the field. The approach is demonstrated for theophylline, but can be used to assay the drug content of any tablet or to determine its dissolution or disintegration characteristics. The procedure can be used in the field without the need for any instrumentation.

Stability of nitroglycerin tablets submitted by U.S. hospitals.

The stability of nitroglycerin tablets that had been stored in hospitals across the United States was studied. Through a voluntary FDA drug stability program, all hospital pharmacies in the United States were asked in October 1981 to complete a response card indicating information about nitroglycerin tablets they had in stock. Based on the responses, FDA selected 167 samples (representing three manufacturers and all available tablet strengths) from pharmacies that represented an adequate cross section of the country. The samples were analyzed for content uniformity, strength, identification, and disintegration; samples that left a residue on the screen of the tablet disintegration basket were tested for dissolution by three methods and compared with samples that did not leave a residue. All samples met USP requirements for content uniformity, strength, and disintegration. Six samples that showed unusual disintegration characteristics dissolved slowly by one or more methods; however, other samples also showed slow dissolution. Nitroglycerin tablets appear to be stable when stored under actual marketplace conditions. The USP disintegration test will not distinguish between rapidly and slowly dissolving tablets.

Stability of digoxin tablets collected from U.S. hospitals.

The stability of digoxin tablets that had been stored in hospitals across the United States was studied. All hospital pharmacies in the U.S. were contacted in February 1980 to inform them about the program, the reimbursement procedures, the sampling requirement, and the process by which laboratory results would be distributed. A response card was included for those who wanted to participate. Ninety-two samples, representing three manufacturers and an adequate cross-section of the country, as well as typical dosage forms and packaging variations, were selected for laboratory analyses of content uniformity, strength, dissolution, identification, and related fluorescing substances. Eighty-five samples met the current compendial standards and seven samples failed the dissolution specifications. All seven were manufactured before July 1975 when the UPS dissolution requirements were changed. The digoxin products studied were not adversely affected by the variable stresses of the marketplace.