Source apportionment and quantification of liquid and headspace leaks from closed system drug-transfer devices via Selected Ion Flow Tube Mass Spectrometry (SIFT-MS)

Abstract

A system to differentiate and quantify liquid and headspace vapor leaks from closed system drug-transfer devices (CSTDs) is presented. CSTDs are designed to reduce or eliminate hazardous drug (HD) exposure risk when compounding and administering HDs. CSTDs may leak liquid, headspace, or a mixture of the two. The amount of HD contained in liquid and headspace leaks may be substantially different. Use of a test solution containing two VOCs with differences in ratios of VOC concentrations in the headspace and liquid enables source apportionment of leaked material. SIFT-MS was used to detect VOCs from liquid and headspace leaks in the vapor phase. Included in this report is a novel method to determine the origin and magnitude of leaks from CSTDs. A limit of leak detection of 24 μL of headspace vapor and 0.14 μL of test liquid were found using Selected Ion Flow Tube Mass Spectrometry (SIFT-MS).

Evaluation of propylene glycol methyl ether as a potential challenge agent for leak detection of liquid and headspace from closed system drug transfer devices using Fourier transform infrared spectroscopy

“…[4][5][6][7][8][9] Studies in the literature that evaluate leak testing for quantifying CSTD efficacy, oen use a surrogate compound as the detected chemical in place of the HD. [10][11][12] Use of a surrogate can increase the sensitivity of a test compared to using low volatility HDs, which can be difficult to detect in manipulations of CSTDs intended to simulate real world use scenarios, such as when transferring drugs from a vial.…”

“…However, when substituting an HD for a surrogate, in an aqueous environment, vapor pressure and Henry's constant become signicant variables. 10,13 A variation of the NIOSH dra protocol 1 was presented in Wilkinson et al, 12 that used FTIR gas-phase detection of 2-phenoxyethanol (2-POE) from aqueous solutions as a method to detect leaks from CSTDs. Previous work using semi-volatile compounds as leak detection markers suffered from slow evaporation and adsorption losses which complicated or prevented correlating leak volumes with gas phase measurements.…”

“…Previous work using semi-volatile compounds as leak detection markers suffered from slow evaporation and adsorption losses which complicated or prevented correlating leak volumes with gas phase measurements. 10 In our own evaluation of 2-POE, the method seemed to suffer signicant analytical challenges due to the low volatility of 2-POE (2020 research by Westbrook; unreferenced †). Wilkinson suggested that the use of PGME, which is a much more volatile compound than 2-POE, may be an effective indicator of leaks (2020 data presented by Wilkinson to NIOSH; unreferenced ‡).…”