Safe decontamination of cytostatics from the nitrogen mustards family. Part one: cyclophosphamide and ifosfamide

Figures & data

Figure 1 The pathway of conversion of CP in the presence of sodium hypochlorite (5% solution).

Abbreviations: CP, cyclophosphamide; CP-TP1-OCl, 4-hydroxy-cyclophosphamide; CP-TP2-OCl, ifosfamide.

Figure 2 Scheme of degradation CP after reaction with a solution of 0.01 M NaOH.

Abbreviations: CP, cyclophosphamide; CP-TP1-OH, 3-((amino(bis(2-chloroethyl) amino)phosphoryl)oxy) propanoic acid.

Figure 3 The proposed mechanism of adsorption of CP on a titania surface.

Abbreviation: CP, cyclophosphamide.

Figure 4 Transformation products formed during CP degradation plotted as a function of the normalized concentration (C/C₀) of cyclophosphamide decay.

Note: Transformation products formed during the decontamination time (minutes) in the presence of (A) 5% NaClO agent, (B) 0.01 M NaOH agent, and (C) TiO₂.

Abbreviations: CP, cyclophosphamide; CP-TP1-OCl, 4-hydroxy-cyclophosphamide; CP-TP2-OCl, ifosfamide.

Figure 5 The proposed pathway of conversion of IFOS in the presence of a sodium hydroxide (0.01 M) agent.

Abbreviations: IFOS, ifosfamide; IFOS-TP1-OH, ifosforamide mustard.

Figure 6 The proposed pathway of adsorption of IFOS on a titania surface.

Abbreviation: IFOS, ifosfamide.

Figure 7 Transformation products formed during IFOS degradation plotted as a function of the normalized concentration (C/C₀) of IFOS decay.

Note: Transformation products formed during the decontamination time (minutes) in the presence of (A) 5% NaClO agent, (B) 0.01 M NaOH agent, and (C) TiO₂.

Abbreviations: IFOS, ifosfamide; IFOS-TP1-OH, ifosforamide mustard.

Figure 8 The DRIFTS fingerprint spectra of CP destructive adsorption on the titanium oxide.

Abbreviations: CP, cyclophosphamide; DRIFTS, diffuse reflectance infrared Fourier transform spectroscopy.

Figure 9 The DRIFTS fingerprint spectra of IFOS destructive adsorption on the titanium oxide.

Abbreviations: IFOS, ifosfamide; DRIFTS, diffuse reflectance infrared Fourier transform spectroscopy.

Figure 10 The proposed mechanistic pathway of reactive adsorption of CP on a titania surface with DRIFT characteristics.

Abbreviation: CP, cyclophosphamide.

Figure 11 The proposed mechanistic pathway of reactive adsorption of IFOS on a titania surface with DRIFT characteristics.

Abbreviation: IFOS, ifosfamide.

Figure S1 HPLC–MS chromatogram (A) and mass spectra (B) of CP.

Note: Adduction is represented by [M+H]+, formed by the interaction of a molecule with a proton (hydron).

Abbreviations: CP, cyclophosphamide; HPLC–MS, high-performance liquid chromatography–mass spectrometry; NL, intensity of the signal; RT, retention time.

Figure S2 HPLC–MS chromatogram (A) and mass spectra of the transformation product of CP (B) 4-hydroxycyclophosphamide and (C) 3-(2-chloroethyl)-2-((2-chloroethyl) amino)-1,3,2-oxazaphosphinane 2-oxide (IFOS) from CP in sodium hypochlorite 5% solution (NaClO).

Note: Adduction is represented by [M+H]+, formed by the interaction of a molecule with a proton (hydron).

Abbreviations: CP, cyclophosphamide; HPLC–MS, high-performance liquid chromatography–mass spectrometry; NL, intensity of the signal; RT, retention time.

Figure S3 HPLC–MS chromatogram (A) and mass spectra (B) of transformation product 3-((amino(bis(2-chloroethyl)amino)phosphoryl)oxy) propanoic acid from CP in sodium hydroxide 0.01 M (NaOH) solution.

Note: Adduction is represented by [M+H]+, formed by the interaction of a molecule with a proton (hydron).

Abbreviations: CP, cyclophosphamide; HPLC–MS, high-performance liquid chromatography–mass spectrometry; NL, intensity of the signal; RT, retention time.

Figure S4 Typical LC–MS chromatogram (A) and mass spectra (B) of IFOS.

Note: Adduction is represented by [M+H]⁺, formed by the interaction of a molecule with a proton (hydron).

Abbreviations: IFOS, ifosfamide; LC–MS, liquid chromatography–mass spectrometry; NL, intensity of the signal; RT, retention time.

Figure S5 LC–MS chromatogram (A) and mass spectra (B) of the transformation product IFOS-TP1-OH of IFOS in sodium hydroxide 0.01 M (NaOH) solution.

Note: Adduction is represented by [M+H]⁺, formed by the interaction of a molecule with a proton (hydron).

Abbreviations: IFOS, ifosfamide; IFOS-TPI-OH, 3-((amino(bis(2-chloroethyl)amino)phosphoryl)oxy) propanoic acid; LC–MS, liquid chromatography–mass spectrometry; NL, intensity of the signal; RT, retention time.