Hplc/Electrospray Ionization Mass Spectrometric Analysis of the Heterocyclic Aromatic Amine Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Human Milk

Abstract

A new procedure has been developed for the extraction of 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and other heterocyclic aromatic amines from human breast milk samples. Extracts were analyzed by high-performance liquid chromatography/electrospray ionization/tandem mass spectrometry (HPLC/ESI-MS/MS) with selective reaction monitoring detection. Tandem ESI-MS/MS detection provides much improved sensitivity and specificity, compared with those of a previous method that used selected ion monitoring. Milk samples were collected from 48 healthy volunteers, including five vegetarians. Donors completed a detailed dietary questionnaire. The concentrations of PhIP in the milk samples were low and below the limit of quantification (0.68 pg/mL) for all subjects except one, for whom a concentration of 1.0 pg PhIP/mL was measured. Our results indicate that the levels of PhIP in human milk are substantially lower than what was previously reported.

The Cooked Meat Carcinogen 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine Activates the Extracellular Signal–Regulated Kinase Mitogen-Activated Protein Kinase Pathway

“…A major role of the MAPK ERK pathway is to modulate gene transcription involved in cell proliferation and migration, and ERK activation has been reported in human mammary and prostate cancer tissues (23,24). Given that consumption of cooked meat can lead to low levels of PhIP being present in body fluids such as breast milk (25), it is possible that PhIP may exert estrogenic and mitogenic effects in humans that could contribute to carcinogenesis.…”

Review on the analysis of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and its phase I and phase II metabolites in biological matrices, foodstuff and beverages

“…For the analyses of PhIP and its metabolites various techniques were used for the separation of ions, formed upon ionization: a single quadrupole mass spectrometer [47,56], a quadrupole-time-of-flight [13], a triple quadrupole [32,33,40,42,50,54,56,[61][62][63][64][65][66][67][68][69][70], an ion trap [11,29,34,37,48,49,[71][72][73][74], a double focussing instrument [43,72] and an accelerator mass spectrometer [41]. Low quantification limits (pg/g or pg/mL) were reached using mass spectrometry as a detection technique.…”

Analytical methods applied to the determination of heterocyclic aromatic amines in foods

“…Some authors [4,5,29,105,110,114] replace the PRS and C 18 cartridges with a cation exchange Oasis MCX extraction cartridge, which is connected in series to the Extrelut-20 resin. This allows the recovery of all the HAAs in one fraction.…”

“…They are also present in cooking fumes [7,8], several foods [9,10], coffee [11], alcohol beverages [10,12], and from environmental sources, such as cigarette smoke [13][14][15][16][17], air [13], river and rainwater [18,19]. Also, some HAAs have been detected in human tissues [20], hair [21] and in biological fluids, such as plasma, urine or bile [3,[22][23][24][25][26][27], as well as in milk of healthy women [28,29].…”