Detecting Antihistamines in Milk Using UHPLC-QE HF HRMS


Scientists from the Chinese Academy of Agricultural Sciences in Beijing, China developed a new method for detecting 20 antihistamines in raw cow’s milk samples using high-field quadrupole Orbitrap high resolution mass spectrometry (UHPLC-QE HF HRMS) combined with dispersive micro solid phase extraction (DMSPE). Their findings were published in the Journal of Chromatography A (1).

Can container milk with cow milking facility and mechanized milking equipment in the milking hall | Image Credit: © thanapun -

Can container milk with cow milking facility and mechanized milking equipment in the milking hall | Image Credit: © thanapun -

This method was applied to 205 collected cow’s milk samples, with eight antihistamines being detected in 16 milk samples. There were 28.2 μg/L~157.9 μg/L of chlorphenamine, 254 μg/L of cyproheptadine, and of 25.7 μg/L promethazine in the samples.

Antihistamines are medicines that are typically used to relieve allergy symptoms, such as hives, hay fever, and reactions to insect bites (2). They are antagonists of histamine receptors and are divided into three main groups, otherwise known as generations: first-generation, which can pass into the brain more easily and are more likely to cause drowsiness, second-generation, which are newer and less likely to cause drowsiness, and third-generation, which are made from second-generation antihistamines and are even less likely to cause drowsiness (3).

Due to the antiemetic, sedative, and hypnotic effects of antihistamines, these medications have been illegally used for animal breeding to promote growth and treat inflammation and allergies. Additionally, antihistamines can be used as veterinary drugs to reduce the pressure and mortality during animal transportation, treat diseases, and improve the efficacy of antibacterials.

However, antihistamines have strong central nervous system inhibitory effects, with some second-generation antihistamines having been found to have significant cardiac toxicity. Moreover, antihistamines can be excreted into milk during breastfeeding. Exposure to antihistamines during breastfeeding can lead to irritability, colic, sleepiness, and in extreme cases can lead to death. There have only been a handful of published studies focused on the levels of antihistamine residue in milk and the evaluation of risks due to deficiency of trace analysis methods, according to the scientists (1).

Various methods have been developed for tracking antihistamines in water, blood, urine, and drug formulations; however, there is very little literature describing the determination of antihistamines in milk, using techniques like gas chromatography-flame ionization detector (GC-FID), radioimmunoassay (RIA), and GC–mass spectrometry (GC–MS). Using these with a traditional detector can make it difficult to detect trace antihistamines due to the presence of additional interference peaks and low concentrations of analytes from the milk matrix.

In the Journal of Chromatography A study,the scientists determined the limit of detection (LOD) for 20 antihistamines in milk ranged from 0.05 µg/L to 1.0 µg/L. Recoveries were between 80.7% and 108.3%, with the relative standard deviation being less than 15%. The scientists found 1.3 μg~8.5 μg/L of chlorphenamine, diphenhydramin, desloratadine, cetirizine, loratadine, and ebastine were found in 11 milk samples. These residuals could have stemmed from antihistamine use in animal husbandry, pollution during breeding, antihistamine residues in feed and drinking water, or the breeding environment.

Altogether, this proposed method proved suitable for confirmatory monitoring and quantitative analysis of antihistamines in milk. This may be noteworthy for protecting human health and fighting environmental pollution. However, further research is needed, as antihistamines in cow’s milk has not been extensively studied. Existing detection methods are not yet being specific or sensitive enough to accurately detect these residues, the scientists wrote. Further studies could help develop a better understanding of the impact of antihistamine residues on human health.


(1) Decheng, S.; Zhanteng, S.; Zhiming, X.; et al. Trace Analysis of 20 Antihistamines in Milk by Ultrahigh Performance Liquid Chromatography Coupled with High Field Quadrupole Orbitrap High Resolution Mass Spectrometry Followed Dispersive Micro Solid Phase Extraction. J. Chromatogr. A 2024, 1727, 464989. DOI: 10.1016/j.chroma.2024.464989

(2) Antihistamines. Crown 2024. (accessed 2024-6-17)

(3) Foley, K. Benadryl, Zyrtec, and More: A List of 7 Antihistamines. GoodRx, Inc 2024. (accessed 2024-6-17)

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