Acta Scientific Pharmaceutical Sciences (ASPS)(ISSN: 2581-5423)

Research Article Volume 4 Issue 11

Quantification of Cyclobenzaprine in Human Plasma by LC/MS/MS and its Pharmacokinetics Application

Mohamed Raslan1,2, Sara AR1, Eslam MS1and Nagwa A Sabri2*

1Drug Research Centre, Cairo, Egypt
2Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

*Corresponding Author: Nagwa A Sabri, Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

Received: October 08, 2020; Published: October 30, 2020

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Abstract

Background: Cyclobenzaprine is a skeletal muscle relaxant used in management of focal muscular disturbances and as an adjunct to physical therapy for relief of muscle spasm.

Aim: Establishment of a bio-analytical method in order to quantify cyclobenzaprine in plasma and investigate cyclobenzaprine pharmacokinetics in human plasma and its application in clinical studies including comparative bioavailability studies.

Methods: After extraction of cyclobenzaprine from plasma, analysis was performed with mobile phase ratio of acetonitrile: 0.1% formic acid 90:10 at a flow rate of 0.5 ml/min, ESI positive mode, and m/z 276.6à216.4 for cyclobenzaprine, and 325.1à109 for escitalopram (IS). The bioequivalence study was involving 24 volunteers in a crossover pattern. Pharmacokinetic parameters AUC0-t, AUC0-inf, Cmax and Tmax used for assessment of bioequivalence of the generic and reference products.

Results: The developed bioanalytical method showed that the average recovery of cyclobenzaprine from plasma was 82.883%, LLOQ 0.05 ng/ml. Correlation coefficient (r2) 0.9998. Analysis of variance showed that there was no significant difference between generic and reference products.

Conclusion: The established LC/MS/MS method is fully validated for the determination of cyclobenzaprine in biological samples and is suitable for clinical pharmacokinetic studies, clinical trials and monitoring drug levels in plasma to ensure clinical efficacy and safety, avoid therapeutic failure or incidence of adverse events. Moreover, generic product was found to provide the same rate and extent of drug absorption as the reference product.

Keywords: Cyclobenzaprine; LC/MS/MS; Muscle Spasm; Sustained Release Capsule; Therapeutic Drug Monitoring

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References

  1. Alison Brayfield. “Martindale-The Complete Drug Reference” 38th edition, Pharmaceutical Press, London, UK (2014): 2023.
  2. Katz WA., et al. “Cyclobenzaprine in the treatment of acute muscle spasms: review of a decade of clinical experience”. Clinical Therapeutics 10 (1988): 216-228.
  3. De Lee JC., et al. “Skeletal muscle spasm and a review of muscle relaxants”. Current Therapeutic Research 27 (1980): 64-74.
  4. “Extended-release cyclobenzaprine (Amrix)”. The Medical Letter 49 (2007): 102-103.
  5. Van Tulder MW., et al. “Muscle relaxants for non-specific low back pain”. Cochrane Database of Systematic Reviews 2 (2003): CD004252.
  6. Chou R., et al. “Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review”. Journal of Pain and Symptom Management 2 (2004): 140-175.
  7. Highlights of Prescribing Information, AMRIX® (cyclobenzaprine hydrochloride extended-release capsules), for oral use, approved by the U.S. Food and Drug Administration, AMRIFU-001 (2019).
  8. AMRIX® (Cyclobenzaprine Hydrochloride Extended-Release Capsules), N021777/S-012, AMR-005, (2013).
  9. Darwish and Xie. Comparison of the Single-Dose Pharmacokinetics of Once-Daily Cyclobenzaprine Extended-Release 30 mg and Cyclobenzaprine Immediate-Release 10 mg Three Times Daily in the Elderly”. Drugs Aging2 (2009): 95-101.
  10. D Faber. Journal of Chromatography A 12 (1974): 675.
  11. H Hucker and S Stauffer. Journal of Chromatography A 124 (1976): 164.
  12. Constanzer, et al. Journal of Chromatography A 339 (1985).
  13. P Hwang., et al. Journal of Liquid Chromatography 16 (1993): 1163.
  14. Constanzer M., et al. “Development and comparison of high-performance liquid chromatographic methods with tandem mass spectrometric and ultraviolet absorbance detection for the determination of cyclobenzaprine in human plasma and urine”. Journal of Chromatography B 666 (1995): 117e126.
  15. Darwish M., et al. “Single-dose pharmacokinetics of once-daily cyclobenzaprine extended release 30 mg versus cyclobenzaprine immediate release 10 mg three times daily in healthy young adults: a randomized, open-label, two period crossover, single-centre study”. Clinical Drug Investigation 28 (2008): 793e801.
  16. Brioschi TM., et al. “Pharmacokinetics and bioequivalence evaluation of cyclobenzaprine tablets”. BioMed Research International (2013): 281392.
  17. , et al. “Quantitative Determination of Cyclobenzaprine In Human Plasma By High Pressure Liquid Chromatography”. Journal of Liquid Chromatography 16.5 (1993): 1163-1171.
  18. Tatiane Maria de Lima Souza Brioschi., et al. “Pharmacokinetics and Bioequivalence Evaluation of Cyclobenzaprine Tablets”. Bio Med Research International (2013).
  19. M Constanzer., et al. “Development and comparison of high-performance liquid chromatographic methods with tandem mass spectrometric and ultraviolet absorbance detection for the determination of cyclobenzaprine in human plasma and urine”. Journal of Chromatography B 666 (1995): 117-126.
  20. Wenhong Yu., et al. “Rapid and sensitive analysis of cyclobenzaprine by LC/MS/MS: Application to a pharmacokinetic study of cyclobenzaprine in dog”. Asian Journal of Pharmaceutical Sciences 9 (2014): 117-122.
  21. Y Xiang., et al. “Determination of cyclobenzaprine in human plasma by liquid chromatography electrospray ionization tandem mass spectrometry and its application in a pharmacokinetic study”. Biomedical Chromatography (2011).
  22. Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study (2013).
  23. Guidance for Industry Bioanalytical Method Validation (2018).
  24. Guidance for Industry, Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA (2013).
  25. Ronilson A Moreno., et al. “Comparative Bioavailability and Pharmacodynamic Aspects of Cyclobenzaprine and Caffeine in Healthy Subjects and the Effect on Drowsiness Intensity”. Journal of Bioequivalence 3 (2009): 086-092.
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Citation

Citation: Nagwa A Sabri., et al. “Quantification of Cyclobenzaprine in Human Plasma by LC/MS/MS and its Pharmacokinetics Application". Acta Scientific Pharmaceutical Sciences 4.11 (2020): 90-96.




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