Establishment and validation of analytical methods for 15 hazardous drugs by UPLC-Q/Orbitrap-HRMS

Abstract

Background: Cytotoxic drug residues in pharmacy intravenous admixture services (PIVAS) have always been a major problem for pharmaceutical workers and the PIVAS environment,which is not only pollutes the PIVAS environment, but also causes serious harm to the life and health of the staff. This study aimed to establish an ultra-high performance liquid chromatography quadrupole orbitrap high resolution mass spectrometry (UPLC-Q/Orbitrap-HRMS) method for the rapid detection and monitor of 15 cytotoxic drugs.Methods: UPLC-Q/Orbitrap-HRMS method was used to establish a rapid detection method for 15 cytotoxic drugs such as cytarabine, gemcitabine and so on. The daily precision and accuracy of this method were verified by injecting four concentrations of standard solution on the same day, and the same four concentrations of standard solution were injected within three days respectively to verify the daily precision of this method. The signal-to-noise ratio (SNR) of 10:1 was calculated as the limit of quantity.The mixed standard solution of 15 cytotoxic drugs with concentrations of 0.5, 1, 3, 10, 30, 100, 300, and 1,000 ng/mL was configured and detected by this method for linearity and range.The stability of this method was investigated using a mixture of 15 drugs (15MIX) standard solutions at high concentration (300 ng/mL) and low concentration (10 ng/mL) at room temperature for 12 and 24 hours, respectively. A standard solution of each drug, 15MIX and blank solution were taken to verify the exclusivity of the method. Results:The results showed that the method had good specificity, and the intraday precision of all drugs was less than 10% and the intraday precision was less than 15%. At the same time, the standard curve had good linearity, R 2 was greater than 0.99, and the limit of quantification of most drugs was about 1 ng/mL. Conclusions:In this study, an UPLC-Q/Orbitrap-HRMS method was established for the rapid detection of 15 cytotoxic drugs, providing technical support for the monitoring of cytotoxic drug residues in PIVAS, which is of great significance for environmental contamination mornitoring as well as occupational exposure alert.

Real-world study of the leakage of two types of infusion bags in multicenter pharmacy intravenous admixture service (PIVAS)

“…Occupational exposure to drugs and its association with adverse health effects has been well demonstrated over the decades, especially antineoplastic drugs (Yu et al, 2022). Previous studies have demonstrated that the environmental pollution caused by leakage causes physiological damage to PIVAS staff, and long-term occupational exposure also causes injuries to staff, especially for cytotoxic drugs (Connor et al, 2014;Hao et al, 2022).…”

“…Raveena confirmed that environmental contamination plays a role in biological exposure to cyclophosphamide (Raveena et al, 2015). Some studies focused on antineoplastic drug residue monitoring, for example, ultra-high pressure liquid chromatography separation coupled to tandem mass spectrometry detection (UHPLC-MS/MS) methods for the detection of surface samples (Fleury et al, 2022), ultra-high performance liquid chromatography quadrupole orbitrap high resolution mass spectrometry (UPLC-Q/Orbitrap-HRMS) method for the rapid detection and monitor of 15 cytotoxic drugs in PIVAS (Yu et al, 2022). Other studies focused on the health risks associated with occupational exposures to antineoplastic drugs, and the findings were generally indicative of an increased risk of adverse reproductive outcomes with occupational exposure (Connor et al, 2014).…”

Statistical analysis of the storage time of finished product infusion

“…Moreover, prolonged placement of finished infusion solutions can decrease drug concentrations, preventing the timely achievement of effective therapeutic concentrations and increasing the risk of bacterial resistance. [16][17][18] Therefore, leaving a finished infusion with unstable properties for too long may cause drug degradation and affect the drug's therapeutic effect. The number of particles in the infusion may also increase and the physical and chemical properties of the infusion may change, resulting in outcomes such as discoloration and precipitation.…”