Abstract
Baclofen was illegally used in veterinary clinical medicine as a growth-promoting agent. To date, few methods have been developed for the monitoring of baclofen in animal tissues. In this study, a sensitive and efficient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to identify and quantify baclofen in the muscle, liver, kidney, and fat of swine was developed and validated. Baclofen was extracted from tissues with ammonium acetate buffer (pH 5.2) and isolated with isopropyl-ethyl acetate (4:6, v/v). Then, a solid phase extraction using MCX cartridge was used to clean up the extracts. The elution was evaporated to dryness and reconstituted with water/methanol (90:10 v/v). All samples were determined by LC-MS/MS system through positive ionization in a multiple reaction monitoring (MRM) mode. The proposed method was validated by evaluation of specificity, linearity, recovery, accuracy, precision, LOD, and LOQ values according to Commission Decision 2002/657/EC. Estimated limit of quantification for baclofen in the muscle, liver, kidney, and fat of this method was 1.00 μg/kg, respectively. The mean intra- and inter-day assay accuracies fell within a range 88.5–93.9% and 86.2–93.2%, respectively. The mean intra- and inter-day precisions were 1.78 and 4.95% (RSD < 15%), respectively. The proposed method has proved to be suitable for accurate quantitative determination of baclofen for residue analysis.
References
Batt AL, Aga DS (2005) Simultaneous analysis of multiple classes of antibiotics by ion trap LC/MS/MS for assessing surface water and groundwater contamination. Anal Chem 77(9):2940–2947. doi:10.1021/ac048512+
Bhushan R, Dixit S (2012) HPLC enantioresolution of (R,S)-baclofen using three newly synthesized dichloro-s-triazine reagents having amines and five others having amino acids as chiral auxiliaries. Biomedical chromatography : BMC 26(6):743–748. doi:10.1002/bmc.1723
De Giovanni N, d'Aloja E (2001) Death due to baclofen and dipyrone ingestion. Forensic Sci Int 123(1):26–32
Flardh M, Jacobson BM (1999) Sensitive method for the determination of baclofen in plasma by means of solid-phase extraction and liquid chromatography-tandem mass spectrometry. J Chromatogr A 846(1–2):169–173
Goda R, Murayama N, Fujimaki Y, Sudo K (2004) Simple and sensitive liquid chromatography-tandem mass spectrometry method for determination of the S(+)- and R(−)-enantiomers of baclofen in human plasma and cerebrospinal fluid. J Chromatogr B Anal Technol Biomed Life Sci 801(2):257–264
Hou XL, Wu YL, Chen RX, Zhu Y, Lv Y, Xu XQ (2014) Evaluation of two modified quick, easy, cheap, effective, rugged and safe (QuEChERS) sample preparation methods for the analysis of baclofen and gabapentin in feeds by liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal 88:53–59. doi:10.1016/j.jpba.2013.08.026
Jafari MT, Khayamian T, Shaer V, Zarei N (2007) Determination of veterinary drug residues in chicken meat using corona discharge ion mobility spectrometry. Anal Chim Acta 581(1):147–153. doi:10.1016/j.aca.2006.08.005
Kamendi H, Barthlow H, Lengel D et al (2016) Quantitative PK/PD modeling of baclofen-mediated cardiovascular effects using blood pressure and heart rate in rats. Br J Pharmacol. doi:10.1111/bph.13561
Kaufmann A (2009) Validation of multiresidue methods for veterinary drug residues; related problems and possible solutions. Anal Chim Acta 637(1–2):144–155. doi:10.1016/j.aca.2008.09.033
Kiel LB, Hoegberg LC, Jansen T, Petersen JA, Dalhoff KP (2015) A nationwide register-based survey of baclofen toxicity. Basic & clinical pharmacology & toxicology 116(5):452–456. doi:10.1111/bcpt.12344
Kim TH, Shin S, Shin JC et al (2013) Liquid chromatography-tandem mass spectrometry determination of baclofen in various biological samples and application to a pharmacokinetic study. J Chromatogr B Anal Technol Biomed Life Sci 938:43–50. doi:10.1016/j.jchromb.2013.08.030
Liu ZY, Yang K, Chen FH et al (2015) Development of a rapid method for the confirmatory analysis of flunixin residue in animal tissues using liquid chromatography-tandem mass spectrometry. Food Anal Method 8(2):352–362. doi:10.1007/s12161-014-9901-z
Nahar LK, Cordero RE, Nutt D et al (2016) Validated method for the quantification of baclofen in human plasma using solid-phase extraction and liquid chromatography-tandem mass spectrometry. J Anal Toxicol 40(2):117–123. doi:10.1093/jat/bkv125
Pedron VT, Varani AP, Balerio GN (2016) Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice. Synapse 70(5):187–197. doi:10.1002/syn.21886
Perry HE, Wright RO, Shannon MW, Woolf AD (1998) Baclofen overdose: drug experimentation in a group of adolescents. Pediatrics 101(6):1045–1048
Radhakrishnan H (2016) Baclofen-induced neurotoxicity in a patient with end-stage renal disease. Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia 27(3):595–597. doi:10.4103/1319-2442.182437
Singh M, Bhushan R (2016) HPLC enantioseparation of racemic bupropion, baclofen and etodolac: modification of conventional ligand exchange approach by ‘pre-column formation of chiral ligand exchange complexes’. Biomedical chromatography : BMC. doi:10.1002/bmc.3746
Sioufi A, Kaiser G, Leroux F, Dubois JP (1988) Determination of the S(+)- and R(−)-enantiomers of baclofen in plasma and urine by gas chromatography using a chiral fused-silica capillary column and an electron-capture detector. J Chromatogr 450(2):221–232
Szpot P, Chlopas A, Buszewicz G, Teresinski G (2016) Application of high-resolution mass spectrometry to determination of baclofen in a case of fatal intoxication. Forensic toxicology 34:268–276. doi:10.1007/s11419-016-0314-0
Thill C, Di Constanzo L, Pessey F et al (2016) Self-induced drug intoxication in baclofen: of the calm hypotonic coma in the status epilepticus. Ann Biol Clin 74(3):348–352. doi:10.1684/abc.2016.1148
Acknowledgements
This study was supported by the Hunan Graduate Innovation Project (CX2014B307), and this work was co-funded by the Institute of Hunan Province Veterinary Drugs and Feed Supervision.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of Interest
Kun Yang declares that he has no conflict of interest. Yu-Jun Zhou declares that he has no conflict of interest. Fu-Hua Chen declares that he has no conflict of interest. Xue-Ming Long declares that he has no conflict of interest. Guang-Wei Kuang declares that he has no conflict of interest. Zhi-Liang Sun declares that he has no conflict of interest. Zhao-Ying Liu declares that he has no conflict of interest.
Ethical Approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed Consent
Not applicable.
Rights and permissions
About this article
Cite this article
Yang, K., Zhou, YJ., Chen, FH. et al. Determination of Baclofen Residue in Muscle, Liver, Kidney and Fat of Swine by Liquid Chromatography-Tandem Mass Spectrometry. Food Anal. Methods 10, 3866–3873 (2017). https://doi.org/10.1007/s12161-017-0958-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12161-017-0958-3