Simultaneous determination of five cytotoxic drugs in surface wiped samples using liquid chromatography and tandem mass spectrometry for the control of environmental contamination in a comprehensive cancer centre

Figures & data

Table 1. Chemical structure and molecular formula of the cytotoxic drugs selected for environmental contamination monitoring

Cytotoxic drug	Molecular formula	Molecular structure
5-Fluorouracil (5FU)	C4H3FN2O2
Gemcitabine (GEM)	C9H11F2N3O4
Cyclophosphamide (CP)	C7H15Cl2N2O2P
Epirubicin (EPI)	C27H29NO11
Paclitaxel (PAC)	C47H51NO14

Figure 1. Typical MRM chromatograms of cytotoxic drugs, obtained from a quality control with 100 ng/mL of 5-fluorouracil and 50 ng/mL of other analytes.

Table 2. MS/MS parameters and m/z transitions for cytotoxic drugs selected in study

Drug	Ionisation mode	Scan event	Acquisition time (min)	MRM Transition(m/z)	Collision energy (eV)	Mean RT (min)
5FU	[M-H]-	1	0.2–0.5	128.8/41.8	14	0.34
GEM	[M + H]+	1	0.2–0.5	263.9/111.9	20	0.33
				263.9/94.8	42
EPI	[M + H]+	2	1.3–1.8	544.1/129.9	20	1.58
				544.1/396.9	16
CP	[M + H]+	2	1.3–1.8	260.8/139.9	26	1.66
				260.8/119.8	22
PAC	[M + H]+	3	1.8–2.2	854.2/285.9	20	1.92
				854.2/509.0	18

Table 3. Linearity parameters and limits of quantification for the analytes

Drug	Calibration range (ng/mL)	r^2	Measured LQ (n = 5) (mean ± S.D., ng/mL)	Accuracy (%RE)	Precision (%RSD)
5FU	5–100	0.996045	4.90 ± 0.38	−2.1	7.8
GEM	1–50	0.995793	0.92* ± 0.07	−8.3	7.9
EPI	1.5–50	0.999171	1.51 ± 0.06	0.9	4.1
CP	1–50	0.999325	0.98 ± 0.06	−1.6	6.4
PAC	1–50	0.999581	1.08 ± 0.05	8.0	4.6

*n = 4

Table 4. Intra-day and inter-day accuracy and precision for the analytes

		Intra-day (n = 5)			Inter-day (n = 25)
Drug	Quality controls (ng/mL)	Mean measured concentration (X ± SD, ng/mL)	Bias (%)	CV (%)	Mean measured concentration (X ± SD, ng/mL)	Bias (%)	CV (%)
5FU	5	4.88 ± 0.25	−2.5	5.1	4.76 ± 0.49	−4.8	10.2
	15	15.52 ± 1.19	3.5	7.7	15.05 ± 096	0.3	6.3
	25	25.38 ± 0.59	1.5	2.3	25.32 ± 1.68	1.3	6.6
	100	95.69 ± 2.68	−4.3	2.8	98.76 ± 3.67	−1.2	3.7
GEM	1	1.02 ± 0.05	1.8	4.8	0.96 ± 0.07	−4.2	7.8
	5	5.06 ± 0.34	1.2	6.7	5.18 ± 0.34	3.7	6.6
	15	14.66 ± 0.40	−2.3	2.7	15.05 ± 0.81	0.3	5.4
	50	45.82 ± 1.26	−8.4	2.8	48.09 ± 3.07	−3.8	6.4
EPI	1.5	1.52 ± 0.04	1.2	2.9	1.47 ± 0.12	−1.9	8.0
	5	4.98 ± 0.12	−0.4	2.4	4.95 ± 0.26	−1.0	5.3
	15	14.74 ± 0.41	−1.7	2.8	14.57 ± 0.43	−2.9	3.0
	50	50.76 ± 1.36	1.5	2.7	50.50 ± 0.84	1.0	1.7
CP	1	0.92 ± 0.08	−7.6	9.0	0.95 ± 0.08	−5.1	8.5
	5	5.10 ± 0.25	2.1	4.9	5.08 ± 0.29	1.5	5.8
	15	14.74 ± 0.59	−1.7	4.0	14.92 ± 0.46	−0.5	3.1
	50	49.61 ± 1.46	−0.8	2.9	50.29 ± 1.32	0.6	2.6
PAC	1	1.01 ± 0.04	0.8	3.8	1.01 ± 0.06	1.4	6.1
	5	5.17 ± 0.19	3.4	3.8	5.23 ± 0.18	4.7	3.4
	15	15.03 ± 0.39	0.2	2.6	15.20 ± 0.60	1.3	4.0
	50	50.33 ± 0.34	0.7	0.7	50.44 ± 1.42	0.9	2.8

Table 5. Short-term stability and in auto-sampler of quality control samples

		Autosampler stability 24 h at 10°C, (n = 5)	Short-term stability 48 h at (2–8) °C, (n = 3)
Drug	Quality controls (ng/mL)	Bias (%)	Bias (%)
5FU	5	−1.3	-
	15	5.0	4.5
	25	−5.6	-
	100	−0.4	13.8
GEM	1	−4.8	-
	5	14.9	−10.8
	15	8.6	-
	50	5.6	−10.2
EPI	1.5	2.7	-
	5	7.8	−3.2
	15	2.1	-
	50	4.9	13.5
CP	1	−9.4	-
	5	−0.1	−10.7
	15	−0.8	-
	50	−0.2	−1.0
PAC	1	5.4	-
	5	13.0	11.5
	15	7.1	-
	50	2.6	8.8

Table 6. Mean recoveries of the target cytotoxic drugs after their spreading on 100cm2 areas of stainless steel surfaces and polyethylene bag surfaces

Drug	Stainless steel surface		Polyethylene bag
	Recovery (%)	CV(%)	Recovery (%)	CV(%)
5FU	38	5.80	37	3.73
GEM	36	9.83	36	12.42
EPI	49	7.21	52	5.45
CP	104	2.16	105	5.18
PAC	105	7.11	89	2.04