Development of Liquid-Chromatography Tandem-Mass-Spectrometry Method for Determining Environmental Contamination by Powdered Medicinal Drugs in Pharmacies

Abstract

The environment and personnel are both exposed to powdered pharmaceuticals inside pharmacies. This makes developing new methods for rapidly determining such contaminants an important objective. In this study, we developed a liquid-chromatography tandem-mass-spectrometry (LC-MS/MS) method for the simultaneous qualitative and quantitative determination of powdered medicinal drugs, such as famotidine, risperidone, lansoprazole, olanzapine, haloperidol, clarithromycin, promethazine, levomepromazine, and chlorpromazine. The method involves the use of acetaminophen as the internal standard, an LC-MS/MS method with a core-shell column, and a 10 mM ammonium formate/acetonitrile gradient mobile phase. The analytes were separated within 14 min, and MS with an electrospray ionization source in positive-ion mode was used. The limits of detection for the 9 drugs were .1-8.4 ng/mL. Linear calibration curves in the 10-50 000 ng/mL range were constructed, and inter-day accuracies of 92.6-113.8% were determined for the 9 drugs. The coefficients of variation were less than 14.6%. These data suggest that the proposed method is applicable for the routine assaying of powdered-medicine contamination in pharmacies.

Keywords: core–shell column; environmental contamination; liquid-chromatography tandem-mass-spectrometry; pharmacy; powdered medicinal drugs.

Figure 1.

Setting the measurement points for suspended-particle concentrations in a hospital dispensary (more than 450 hospital beds, dispensary floor space of about 72 m², and an average of 50 powdered-drug prescriptions dispensed per day).

Figure 2.

Mass spectra of authentic standards.

Figure 3.

Representative total ion chromatograms for a Kinetex C18 (a) and an XBridge C18 (m) column, and multiple reaction monitoring chromatograms of: (b-k) authentic standards (100 ng/mL) and (l) air at the sampling point, using a core–shell ODS column as described in the Methods section.