Abstract
Glycyrrhizic acid (GZA) and glycyrrhetinic acid (GRA) can be determined rapidly and precisely by high-performance liquid chromatography (HPLC) in biological fluids and tissues from exprimental animals and humans. From plasma and tissues, GZA and GRA are extracted by organic solvents and the extracts can directly be used for HPLC. From bile or urine, extraction and determination of GZA and GRA are more diffucult due to interfering endogenous compounds and conjugation of GRA with glucuronides or sulfates. Extraction of GZA and GRA from urine or bile can be performed by ion-pairing followed by extraction with organic solvents or by solid phase extraction. GRA conjugates can be determined by chromatographic separation or by pretreatment with β-glucuronidase. The pharmacokinetics of GRA and GZA can be described by a biphasic elimination from the central compartment with a dose-dependent second elimination phase. Depending on the dose, the second elimination phase in humans has a half-life of 3.5 hours for GZA and between 10–30 hours for GRA. The major part of both GRA or GZA is eliminated by the bile. While GZA can be eliminated unmetabolized and undergoes enterohepatic cycling, GRA is conjugated to GRA glucuronide or sulfate prior to biliary excretion. Orally administered GZA is almost completely hydrolyzed by intestinal bacteria and reaches the systematic circulation as GRA.
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