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A comprehensive review of assay methods to determine drugs in breast milk and the safety of breastfeeding when taking drugs

Abstract

Most of the licit and illicit drugs consumed by the breastfeeding woman pass into the milk and can modify the production, volume and composition of the milk, as well as hypothetically have short- and long-term harmful effects on the infant. There is much confusion in the scientific community regarding this issue: should a woman breastfeed her baby while continuing to use prescription drugs and/or drugs of abuse? There are many case reports of clinically significant toxicity in breast-fed infants from some substances used by mothers (such as irritability, vomiting, sedation, respiratory depression, shock), but there are too few data on studies conducted in breastfeeding women and their infants to make a realistic risk assessment. The objective measurement of a drug and/or metabolites in maternal milk is the first step when investigating the amount of drug exctreted in milk and subsequently calculating the daily dose administered to the breast-fed infant. The present review reports the analytical methods developed to detect different drugs in the breast milk, listing the principal characteristics and validation parameters, advantages and disadvantges. Furthermore, the mechanisms of drug transfer into breast milk are discussed, the correlation between the concentration of the drug in breast milk and potential adverse outcomes on the infant are described for each drug, and suggested harm minimization strategies and approved breastfeeding recommendations are indicated.

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Abbreviations

A:

Amphetamines

AAP:

American Academy of Pediatrics

API:

Atmospheric pressure ionization

BZE:

Benzodiazepines

BEG:

Benzoylecgonine

CAF:

Caffeine

COC:

Cocaine

COT:

Cotinine

∆-9-THC:

Delta-9-tetrahydrocannabinol

DAD:

Diode array detector

DDP:

N-Desmethyldoxepin

ECD:

Electron capture detection

EDDP:

2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine

EMDP:

2-Ethyl-5-methyl-3,3-diphenylpyrroline

EME:

Ecgonine methyl ester

EIA:

Enzyme immunoassay

EMIT:

Enzyme multiplied immunoassay technique

ESI:

Electrospray ionization

FID:

Flame ionization detector

FPIA:

Fluorescence polarization immunoassay

GC:

Gas chromatography

t 1/2 :

Half-life

HPLC:

High-performance liquid chromaqtography

LC:

Liquid chromatography

MA:

Methamphetamine

6-MAM:

6-Monoacetylmorphine

MDMA:

3,4-Methylenedioxymethamphetamine

MET:

Methadone

M/P ratio:

Milk/plasma ratio

M6G:

Morphine-6-glucuronide

MS:

Mass spectrometry

MS/MS:

Tandem mass spectrometry

NCI:

Negative chemical ionization mode

NIC:

Nicotine

NPD:

Nitrogen phosphorus detector

PCA:

Patient-controlled analgesia

RIA:

Radioimmunoassay

SSRIs:

Selective serotonin reuptake inhibitors

SPE:

Solid-phase extraction

MS/MS:

Tandem mass spectrometry assay

UV:

Ultraviolet

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Correspondence to Oscar García-Algar.

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Fríguls, B., Joya, X., García-Algar, O. et al. A comprehensive review of assay methods to determine drugs in breast milk and the safety of breastfeeding when taking drugs. Anal Bioanal Chem 397, 1157–1179 (2010). https://doi.org/10.1007/s00216-010-3681-0

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Keywords

  • Biological samples
  • Clinical
  • Biomedical analysis
  • Drug monitoring
  • Drug screening
  • Pharmaceuticals