Forensic Toxicology

, Volume 33, Issue 2, pp 348–354 | Cite as

Identification and quantification of 4′-methoxy-α-pyrrolidinobutiophenone (4-MeOPBP) in human plasma and urine using LC–TOF-MS in an autopsy case

  • Kaori Shintani-IshidaEmail author
  • Mami Nakamura
  • Misa Tojo
  • Nozomi Idota
  • Hiroshi Ikegaya
Original Article


We encountered an autopsy case of a 35-year-old man who drowned in a bathtub. Nine opened packages of designer drugs containing herbal blends, powders, or liquid were found at the scene, implying abuse. The plasma and urine samples of the deceased were analyzed using liquid chromatography–time-of-flight-mass spectrometry (LC–TOF-MS) with MSE. A new synthetic cathinone, 4′-methoxy-α-pyrrolidinobutiophenone (4-MeOPBP), emerged as a suspected component via elemental composition and molecular structure analyses with acquisition of full spectra of the precursor and product ions by MSE mode. The component was finally identified by comparing the mass spectra obtained from the deceased’s samples with those of the reference standard 4-MeOPBP using LC–TOF-MS and gas chromatography–mass spectrometry. Furthermore, 4-MeOPBP was the main component of an opened package labeled “Silver Snow”. The concentrations of 4-MeOPBP in plasma and urine samples were as high as 9.5 and 12 μg/ml, respectively. To our knowledge, this is the first report disclosing 4-MeOPBP in human specimens.


4′-Methoxy-α-pyrrolidinobutiophenone 4-MeOPBP Synthetic cathinone derivative Liquid chromatography–time-of-flight mass spectrometry LC–TOF-MS Human plasma 



We thank Dr. Kanju Saka of the Department of Forensic Medicine, Graduate School of Medicine, at the University of Tokyo for advice on data analysis. This study was supported by JSPS KAKENHI Grant Number 25293162.

Conflict of interest

There are no financial or other relations that could lead to a conflict of interest.

Ethical approval

Informed consent was obtained from all healthy individuals included in the study, who supplied about 1 ml of whole blood and about 10 ml of urine for use as blank materials.


  1. 1.
    Yonamine M, Silva OA (2002) Confirmation of cocaine exposure by gas chromatography–mass spectrometry of urine extracts after methylation of benzoylecgonine. J Chromatogr B 773:83–87CrossRefGoogle Scholar
  2. 2.
    Galloway FR, Bellet NF (1999) Methadone conversion to EDDP during GC–MS analysis of urine samples. J Anal Toxicol 23:615–619PubMedCrossRefGoogle Scholar
  3. 3.
    Rosano TG, Wood M, Ihenetu K, Swift TA (2013) Drug screening in medical examiner casework by high-resolution mass spectrometry (UPLC–MSE-TOF). J Anal Toxicol 37:580–593PubMedCrossRefGoogle Scholar
  4. 4.
    Guale F, Shahreza S, Walterscheid JP, Chen HH, Arndt C, Kelly AT, Mozayani A (2013) Validation of LC–TOF-MS screening for drugs, metabolites, and collateral compounds in forensic toxicology specimens. J Anal Toxicol 37:17–24PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Plumb RS, Johnson KA, Rainville P, Smith BW, Wilson ID, Castro-Perez JM, Nicholson JK (2006) UPLC/MSE; a new approach for generating molecular fragment information for biomarker structure elucidation. Rapid Commun Mass Spectrom 20:1989–1994PubMedCrossRefGoogle Scholar
  6. 6.
    Coppola M, Mondola R (2012) Synthetic cathinones: chemistry, pharmacology and toxicology of a new class of designer drugs of abuse marketed as “bath salts” or “plant food”. Toxicol Lett 211:144–149PubMedCrossRefGoogle Scholar
  7. 7.
    Zaitsu K, Katagi M, Tsuchihashi H, Ishii A (2014) Recently abused synthetic cathinones, α-pyrrolidinophenone derivatives: a review of their pharmacology, acute toxicity, and metabolism. Forensic Toxicol 32:1–8CrossRefGoogle Scholar
  8. 8.
    Borek HA, Holstege CP (2012) Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med 60:103–105PubMedCrossRefGoogle Scholar
  9. 9.
    Murray BL, Murphy CM, Beuhler MC (2012) Death following recreational use of designer drug “bath salts” containing 3,4-methylenedioxypyrovalerone (MDPV). J Med Toxicol 8:69–75PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Namera A, Urabe S, Saito T, Torikoshi-Hatano A, Shiraishi H, Arima Y, Nagao M (2013) A fatal case of 3,4-methylenedioxypyrovalerone poisoning: coexistence of α-pyrrolidinobutiophenone and α-pyrrolidinovalerophenone in blood and/or hair. Forensic Toxicol 31:338–343CrossRefGoogle Scholar
  11. 11.
    Sauer C, Hoffmann K, Schimmel U, Peters FT (2011) Acute poisoning involving the pyrrolidinophenone-type designer drug 4′-methyl-alpha-pyrrolidinohexanophenone (MPHP). Forensic Sci Int 208:e20–e25PubMedCrossRefGoogle Scholar
  12. 12.
    Saito T, Namera A, Osawa M, Aoki H, Inokuchi S (2013) SPME-GC–MS analysis of α-pyrrolidinovaleorophenone in blood in a fatal poisoning case. Forensic Toxicol 31:328–332CrossRefGoogle Scholar
  13. 13.
    Hasegawa K, Suzuki O, Wurita A, Minakata K, Yamagishi I, Nozawa H, Gonmori K, Watanabe K (2014) Postmortem distribution of α-pyrrolidinovalerophenone and its metabolite in body fluids and solid tissues in a fatal poisoning case measured by LC–MS–MS with the standard addition method. Forensic Toxicol 32:225–234CrossRefGoogle Scholar
  14. 14.
    Namera A, Konuma K, Kawamura M, Saito T, Nakamoto A, Yahata M, Ohta S, Miyazaki S, Shiraishi H, Nagao M (2014) Time-course profile of urinary excretion of intravenously administered α-pyrrolidinovalerophenone and α-pyrrolidinobutiophenone in a human. Forensic Toxicol 32:68–74CrossRefGoogle Scholar
  15. 15.
    Minakata K, Yamagishi I, Nozawa H, Hasegawa K, Wurita A, Gonmori K, Suzuki M, Watanabe K, Suzuki O (2014) MALDI-TOF mass spectrometric determination of four pyrrolidino cathinones in human blood. Forensic Toxicol 32:169–175CrossRefGoogle Scholar
  16. 16.
    Hasegawa K, Wurita A, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Suzuki O, Watanabe K (2014) Identification and quantitation of a new cathinone designer drug PV9 in an “aroma liquid” product, antemortem whole blood and urine specimens, and a postmortem whole blood specimen in a fatal poisoning case. Forensic Toxicol 32:243–250CrossRefGoogle Scholar
  17. 17.
    Eiden C, Mathieu O, Cathala P, Debruyne D, Baccino E, Petit P, Peyriere H (2013) Toxicity and death following recreational use of 2-pyrrolidino valerophenone. Clin Toxicol 51:899–903CrossRefGoogle Scholar

Copyright information

© Japanese Association of Forensic Toxicology and Springer Japan 2015

Authors and Affiliations

  • Kaori Shintani-Ishida
    • 1
    Email author
  • Mami Nakamura
    • 1
  • Misa Tojo
    • 1
  • Nozomi Idota
    • 1
  • Hiroshi Ikegaya
    • 1
  1. 1.Department of Forensic Medicine, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan

Personalised recommendations