Abstract
Human milk is a highly complex biological fluid, and it is considered to be the ideal food for infants during their first months of life. On the other hand, licit and illicit substances consumed by the breastfeeding woman can pass into the milk and may cause harmful effects to the infant. Drug extraction from this matrix can be an analytical challenge due to its high protein and lipid content. Since marijuana is the most commonly used illicit drug at the global level, the aim of the present study was to develop a headspace solid-phase microextraction (HS-SPME) method for the determination of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in human breast milk using gas chromatography−mass spectrometry. The limits of detection and quantification were 10 and 20 ng/mL, respectively, for all analytes. Calibration curves were linear over a concentration range of 20.0–200 ng/mL (r 2 = 0.99). Intraday and interday precision was not greater than 13.3% (relative standard deviation), and accuracy bias ranged from 5.5 to 17.9%. One hundred and nine human milk samples were randomly collected and analyzed. Only two samples were confirmed to be THC positive at 20 and 31 ng/mL. CBD was also detected in one milk sample. The present method has shown to be reliable for determination of THC, CBD and CBN in human breast milk in a very low volume sample (0.05 mL). Also, the HS-SPME procedure was demonstrated to be a rather promising, low cost and environmental-friendly technique. In addition, the SPME is very suitable for automated extraction procedure.
Similar content being viewed by others
References
Bergeria CL, Heil SH (2015) Surveying lactation professionals regarding marijuana use and breastfeeding. Breastfeed Med 10:377–380
Ballard O, Morrow AL (2013) Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am 60:49–74
Neville MC, Anderson SM, McManaman JL, Badger TM, Bunik M, Contractor N et al (2012) Lactation and neonatal nutrition: defining and refining the critical questions. J Mammary Gland Biol Neoplasia 17:167–188
World Health Organization (2009) Infant and young child feeding: model chapter for textbooks for medical students and allied health professionals. http://apps.who.int/iris/bitstream/10665/44117/1/9789241597494_eng.pdf. Accessed Jun 2016
Fleishaker JC (2003) Models and methods for predicting drug transfer into human milk. Adv Drug Deliv Rev 55:643–652
Fríguls B, Joya X, García-Algar O, Pllás CR, Vall O, Pichini S (2010) 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
United Nations Office on Drugs and Crime (2016) World drug report 2016. https://www.unodc.org/doc/wdr2016/WORLD_DRUG_REPORT_2016_web.pdf. Accessed June 2016
Substance Abuse and Mental Health Services Administration (2014) Results from the 2013 national survey on drug use and health: summary of national findings. NSDUH Series H-48, HHS Publication No. (SMA) 14_4863. SAMHSA, Rockville
Ko JY, Farr SL, Tong VT, Creanga AA, Callaghan WM (2015) Prevalence and patterns of marijuana use among pregnant and nonpregnant women of reproductive age. Am J Obstet Gynecol 213:201.e1–201.e10
Jansson LM, Bunik M, Bogen DL (2015) Lactation and the marijuana-using mother. Breastfeed Med 10:342–343
Djulus J, Moretti M, Koren G (2005) Marijuana use and breastfeeding. Can Fam Physician 51:349–350
Metz TD, Stickrath EH (2015) Marijuana use in pregnancy and lactation: a review of the evidence. Am J Obstet Gynecol 213:761–778
Huestis MA (2007) Human cannabinoid pharmacokinetics. Chem Biodivers 4:1770–1804
Reece-Stremtan S, Marinelli KA (2015) ABM Clinical protocol #21: guidelines for breastfeeding and substance use or substance use disorder, revised 2015. Breastfeed Med 10:135–141
Hill M, Reed K (2013) Pregnancy, breast-feeding, and marijuana: a review article. Obstet Gynecol Surv 68:710–718
Begg EJ, Duffull SB, Hackett LP, Ilett KF (2002) Studying drugs in human milk: time to unify the approach. J Hum Lact 18:323–332
Esteban M, Castaño A (2009) Non-invasive matrices in human biomonitoring: a review. Environ Int 35:438–449
Bjørhovde A, Halvorsen TG, Rasmussen KE, Pedersen-Bjergaard S (2003) Liquid-phase microextraction of drugs from human breast milk. Anal Chim Acta 491:155–161
Rossi DT, Wright DS (1997) Analytical considerations for trace determinations of drugs in breast milk. J Pharm Biomed Anal 15:495–504
Marchei E, Escuder D, Pallas CR, Garcia-Algar O, Gomez A, Friguls B, Pichini S (2011) Simultaneous analysis of frequently used licit and illicit psychoactive drugs in breast milk by liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal 55:309–316
Menck RA, de Oliveira CDR, de Lima DS, Goes LE, Leyton V, Pasqualucci CA, Muñoz DR, Yonamine M (2013) Hollow fiber-liquid phase microextraction of barbiturates in liver samples. Forensic Toxicol 31:31–36
Kataoka H, Saito K (2011) Recent advances in SPME techniques in biomedical analysis. J Pharm Biomed Anal 54:926–950
Psillakis E, Kalogerakis N (2003) Developments in liquid-phase microextraction. Trends Anal Chem 22:565–574
de Souza Eller SCW, Flaiban LG, Paranhos BAPB, da Costa JL, Lourenço FR, Yonamine M (2014) Analysis of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in urine samples by hollow fiber-liquid phase microextraction and gas chromatography–mass spectrometry in consideration of measurement uncertainty. Forensic Toxicol 32:282–291
dos Santos MF, Ferri CC, Seulin SC, Leyton V, Pasqualucci CAG, Munoz DR, Yonamine M (2014) Determination of antidepressants in whole blood using hollow-fiber liquid-phase microextraction and gas chromatography–mass spectrometry. Forensic Toxicol 32:214–224
Spietelun A, Marcinkowski Ł, de la Guardia M, Namieśnik J (2013) Recent developments and future trends in solid phase microextraction techniques towards green analytical chemistry. J Chromatogr A 1321:1–13
Röhrig L, Meisch HU (2000) Application of solid phase micro extraction for the rapid analysis of chlorinated organics in breast milk. Fresen J Anal Chem 366:106–111
Debruin LS, Josephy PD, Pawliszyn JB (1998) Solid-phase microextraction of monocyclic aromatic amines from biological fluids. Anal Chem 70:1986–1992
Kowalski CH, da Silva GA, Poppi RJ, Godoy HT, Augusto F (2007) Neuro-genetic multioptimization of the determination of polychlorinated biphenyl congeners in human milk by headspace solid phase microextraction coupled to gas chromatography with electron capture detection. Anal Chim Acta 585:66–75
Kowalski CH, Costa JG, Godoy HT, Augusto F (2010) Determination of polychlorinated biphenyls in Brazilian breast milk samples using solid-phase microextraction and gas chromatography-electron capture detection. J Braz Chem Soc 21:502–509
Kowalski CH, da Silva GA, Godoy HT, Poppi RJ, Augusto F (2013) Application of Kohonen neural network for evaluation of the contamination of Brazilian breast milk with polychlorinated biphenyls. Talanta 116:315–321
Kim SR, Halden RU, Buckley TJ (2007) Volatile organic compounds in human milk: methods and measurements. Environ Sci Technol 41:1662–1667
González-Rodríguez MJ, Liébanas FA, Frenich AG, Vidal JM, López FS (2005) Determination of pesticides and some metabolites in different kinds of milk by solid-phase microextraction and low-pressure gas chromatography–tandem mass spectrometry. Anal Bioanal Chem 382:164–172
United Nations Office on Drugs and Crime (UNODC) (2009) Guidance for the validation of analytical methodology and calibration of equipment used for testing of illicit drugs in seized materials and biological specimens. http://www.unodc.org/documents/scientific/validation_E.pdf. Accessed Oct 2013
Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165:216–224
Scientific Working Group for Forensic Toxicology (SWGTOX) (2013) Standard practices for method validation in forensic toxicology. J Anal Toxicol 37:452–474
Armbruster DA, Pry T (2008) Limit of blank, limit of detection and limit of quantitation. Clin Biochem Rev 29(Suppl 1):49–52
Oliveira CDR, Yonamine M, Moreau RLM (2007) Headspace solid-phase microextraction of cannabinoids in human head hair samples. J Sep Sci 30:128–134
Ulrich S (2000) Solid-phase microextraction in biomedical analysis. J Chromatogr A 902:167–194
Pragst F (2007) Application of solid-phase microextraction in analytical toxicology. Anal Bioanal Chem 388:1393–1414
Perez-Reyes M, Wall ME (1982) Presence of Δ9-tetrahydrocannabinol in human milk. N Engl J Med 307:819–820
Acknowledgements
Financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP Grant No. 2014/04107-7 and Grant 2015/15700-3) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) are gratefully acknowledged. We also thank the Poison Control Center of São Paulo for sample collection.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
There are no financial or other relations that could lead to a conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Ethics Protocol Approval nos. 012/CEM/HMARS/2014 and CEP/FCF/732402) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Rights and permissions
About this article
Cite this article
Silveira, G.d., Loddi, S., de Oliveira, C.D.R. et al. Headspace solid-phase microextraction and gas chromatography−mass spectrometry for determination of cannabinoids in human breast milk. Forensic Toxicol 35, 125–132 (2017). https://doi.org/10.1007/s11419-016-0346-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11419-016-0346-5