Comparison of methods for detection of particulate matter in large-volume perenterals.

The particulate matter content of six commonly used types of large-volume parenteral solutions was evaluated using five methods. The five methods were: (1) visual examination with the naked eye under diffuse light, (2) visual examination with a 2.5 diopter lens under diffuse light, (3) examination with a light scattering apparatus, (4) instrumental examination using the Prototron particle counter, and (5) a membrane filtration and microscopic examination technique. The visual methods (1) and (2) proved to be inadequate because of the insensitivity and high degree of subjectivity. The light-scattering apparatus was reasonably accurate and a considerable improvement over the first two techniques. The Prototron instrument was shown to be capable of predicting whether a solution would pass or fail the recently adopted USP-NF standards for particulate matter content, when compared with the membrane filtration and microscopic examination technique. All of the solutions tested were found to contain very low levels of particulate matter in relation to the USP-NF standard. It is recommended that this recently adopted standard be reevaluated with a view toward increased stringency.