Typically,
glycerophospholipids are represented with two
esterified fatty acids. However, by up to 20%, a significant proportion of this
lipid class carries an
ether-linked
fatty alcohol side chain at the sn-1 position, generally referred to as
ether lipids, which shape their specific physicochemical properties. Among those,
plasmalogens represent a distinct subgroup characterized by an sn-1
vinyl-ether double bond. The total loss of
ether lipids in severe peroxisomal defects such as
rhizomelic chondrodysplasia punctata indicates their crucial contribution to diverse cellular functions. An aberrant
ether lipid metabolism has also been reported in multifactorial conditions including
Alzheimer's disease. Understanding the underlying pathological implications is hampered by the still unclear exact functional spectrum of
ether lipids, especially in regard to the differentiation between the individual contributions of
plasmalogens (plasmenyl
lipids) and their non-
vinyl-ether lipid (plasmanyl) counterparts. A primary reason for this is that exact identification and quantification of
plasmalogens and other
ether lipids poses a challenging and usually labor-intensive task. Diverse analytical methods for the detection of
plasmalogens have been developed. Liquid chromatography-tandem mass spectrometry is increasingly used to resolve complex
lipid mixtures, and with optimized parameters and specialized fragmentation strategies, discrimination between
ethers and
plasmalogens is feasible. In this review, we recapitulate historic and current methodologies for the recognition and quantification of these important
lipids and will discuss developments in this field that can contribute to the characterization of
plasmalogens in high structural detail.