Analytical considerations for trace determinations of drugs in breast milk.

Recent scientific and regulatory interest in lacteal excretion of drugs has prompted this review of bioanalytical sample preparation techniques for milk. The composition and properties of milk are reviewed, with emphasis on how the sample preparation is affected. The most important principals of mammary gland pharmacology, including protein binding, ion trapping and liquid solubility, are described. Because adequate milk volume is difficult to obtain from some smaller rodent species, special arrangements for sample collection, control preparation and assay standardization often need to be made. Several commonly-used sample preparation approaches for drugs in milk, including direct injection, dialysis and ultrafiltration, protein precipitation, liquid-liquid extraction, solid-phase extraction and immunoaffinity extraction. Have been reported with varying degrees of success. The advantages and disadvantages of each of these approaches is discussed.