Mass spectral fragmentation of the intravenous anesthetic propofol and structurally related phenols

Abstract

Propofol (2,6-diisopropyl phenol) is a widely used intravenous anesthetic. To define its pharmacokinetics and pharmacodynamics, methods for its quantitation in biological matrixes have been developed, but its pattern of mass spectral fragmentation is unknown. We found that fragmentation of the [M Ϫ H] Ϫ ion (m/z 177) of propofol in both APCI MS/MS and ESI MS/MS involves the stepwise loss of a methyl radical and a hydrogen radical from one isopropyl side chain to give the most intense product ion, [M ϪH Ϫ CH 4 ] Ϫ , at m/z 161. This two-step process is also the preferred mode of fragmentation for similar branched alkyl substituted phenols. This mode of fragmentation of the [M Ϫ H] Ϫ ion is supported by three independent lines of evidence: (1) Ϫ product ion. Phenols with a single straight chain alkyl substituent, in contrast, undergo ␤ elimination of the alkyl radical irrespective of the length of the alkyl chain, yielding the most intense product ion at m/z 106. This product ion represents a special case of a stable intermediary radical for the two-step process described for branched side chains, because further elimination of a hydrogen radical from the ␤ carbon is not possible. as a supplement to regional anesthesia and in critically ill patients confined to intensive care units. The patient loses consciousness 30 to 50 s after receiving the drug and remains asleep for about 4 to 6 min [1,2]. Even though a single dose of propofol has a short duration of action and produces fast recovery from anesthesia, propofol is not metabolized in a few minutes. It is present in blood, adipose tissues, liver, and brain for a few hours, its concentration decreasing with time [4].

Efficient biotransformation of non-steroid anti-inflammatory drugs by endophytic and epiphytic fungi from dried leaves of a medicinal plant, Plantago lanceolata L.

“…As in the case of DIC, the halogenated ring was untouched; MS (Paíga et al, 2015), most probably the isobutyl sidechain is hydroxylated. The found fragmentation pathway was similar to that described for alkyl-phenols in (Bajpai et al, 2005). …”

Quantitative measurement of propofol and in main glucuroconjugate metabolites in human plasma using solid phase extraction–liquid chromatography–tandem mass spectrometry

“…The mass spectral fragmentation of propofol and related phenols such as thymol was thoroughly studied by Bajpai et al [14] who used transitions 177.2 → 161.2 and 149.2 → 133.0 for propofol and thymol, respectively. These transitions correspond to the loss of methane by the sequential loss of CH 3 and H radicals.…”

Characterization of an exception to the ‘even‐electron rule’ upon low‐energy collision induced decomposition in negative ion electrospray tandem mass spectrometry

“…Recently, Bajpai et al [13] reported the formation of the phenoxide radical anion in a CID experiment. The collision energy employed in their experiment was 30-45 eV, i.e.…”

“…[9] Sometimes, when competing reaction exit channels were not available, radical species appeared as the fragmentation products. [13] It was also proposed that a lower reverse activation barrier due to aromatic stabilization might kinetically favor the formation of radical fragments. [9] In almost all of the cases, the 'even-electron rule' was violated, the decomposition of evenelectron precursor ions was achieved by highly energetic EI or high-energy collisional activation.…”