Formaldehyde (FA) is an industrial chemical product that is widely used to manufacture building materials and household products and is released from several sources within indoor environments, such as particle board, household products, and plywood [1]; hence, a large number of workers and inhabitants are inevitably exposed to FA [2]. Initial studies showed that gaseous FA could cause carcinogenic and fetal abnormalities [3], and clinical and epidemiological investigations have found that work-related exposure to FA results in headaches, anxiety, fatigue, sleep disorders, in particular, cognitive disorders [4, 5]. In addition, the results of animal experiments have consistently revealed that gaseous FA exposure induced abnormal behaviors, including spatial memory deficits [6–۸]. Interestingly, abnormal levels of endogenous FA have been detected in humans exposed to exogenous FA [9], as well as in aged mice and rats [10], in healthy older adults with cognitive disorders [11], and in patients suffering from Alzheimer’s disease (AD) [12]. Documentary evidence indicates that a direct intracerebroventricular injection of excess FA into animal models causes central nervous system damage and, in particular, a marked impairment in memory [13–۱۶]. These data strongly support the notion that excess FA in the hippocampus leads to cognitive deficits. In view of the neurotoxic effects of FA, various analytical methods have been developed to detect FA in animal tissues. The earliest determination method for measuring FA in brain tissues (~0.16–۰٫۲۴ mM) was carried out using gas chromatography/mass spectrometry (GC–MS) [17]. Another sensitive method, developed for the detection of FA in the liver, utilized high-performance liquid chromatography with an ultra violet detector (HPLC-UV) [18, 19]. More recently, using a high-performance liquid chromatography with a fluorescence detector (HPLC-Fluo), we found that there was 0.25–۰٫۳۲ mM FA in the hippocampi of normal adult mice and rats [20].