OPEN-ACCESS PEER-REVIEWED
1*Assistant professor, Dadasaheb Balpande college of Pharmacy, New Swami Samartha Dham Mandir, Besa, Nagpur 440037
2*Assistant Professor, Department of Pharmacology, Saheed Rendo Majhi Medical College, Kalahandi
3Department of Biotechnology, Chaudhary Bansi Lal University, Bhiwani (Haryana),
4Associate Professor and HOD, Pharmaceutical Analysis, Konkan Gyanpeeth Rahul Dharkar College of Pharmacy and Research Institute, Dahivali – Parade Vengaon Road, Post – Tiware, Tal: Karjat, Dist: Raigad, Maharashtra, India – 410201.
5Institute, Dahivali – Parade Vengaon Road, Post – Tiware, Tal: Karjat, Dist: Raigad, Maharashtra, India – 410201.
6Associate Professor, Acropolis Institute of Pharmaceutical Education and Research, Indore RGPV university
7Assistant Professor, Pharmacology, Bhima Bhoi Medical College, Balangir, Odisha
Abstract
The bioanalytical method was established and proved by analyzing interferences and recovery tests for serum and free testosterone in the range of 0.025–500 pg/mL, using an internal standard and normalized to the peak area ratio. The calibration curve of the chemiluminescence assay had a very high coefficient of determination of 0.998 when the concentration was in the range of 1-500 ng/mL. The method proved to have satisfactory precision, with RSD values not exceeding 5.2% and accuracy expressed by the range from -3.1% to 4.8% for RE. A pharmacokinetic study was further done in a cross-over manner following single doses under a fasting state. Pharmacokinetic parameters that were assessed include the maximum plasma concentration Cmax of 150 ± 10 ng/mL, the time taken to reach the maximum plasma concentration, the time to maximum concentration, Tmax of 1 hour, and the area under the curve up to 24 hours, AUC0-24 of 850 ± 50 ng·h/mL. The terminal half-life which was determined by linear regression analysis was 6.5 ± 1.2 hours. We see that the Tmax is reduced and the half-life is also short which indicates faster absorption and clearance of the drug. In conclusion, the analytical method was established and optimized for the determination of testosterone in blood plasma samples of males, irrespective of the variation in their testosterone levels. The pharmacokinetic study revealed that the test compound has a fast absorption and elimination profile that conforms to its short T ½. Subsequent research could look into the impact of various dosing schedules on testosterone exposure in light of the above-discussed pharmacokinetic parameters.
Keywords: LC-MS/MS, testosterone, quantitative analysis, method development and validation, pharmacokinetics, human serum.
References
[1]. Bray, Ferlay, Soerjomataram, Siegel, Torre & Jemal, Global cancer statistics 2018: These Global Cancer Incidence and Mortality, also known GLOBOCAN, provides actual and projected incidence and mortality figures for 36 cancers and for 185 countries. CA: Senn, H. (2005). Embryonal carcinoma: A Cancer Journal for Clinicians, 68(6), 394–424. https://doi.org/10.3322/caac.21492
[2]. Chaturvedi, M., Kohli, B., Arora, A. The importance of information security in retaining employees through techniques used by enron’, International Journal of Management Cases, Vol. 15, No. 2, 01/2013. The Pharma Review Magazine. https://www.pharmareview.info/article/bioan alytical-method-development-for-small- molecule-drugs/62/
[3]. Dams, D., Huestis, Huestis, Huestis, Huestis, Huestis, Huestis, Huestis, Huestis, Huestis Lambert, Lambert, Lambert, Lambert, Lambert & Murphy (2017). Matrix effects in bio-analysis of illicit drugs with LC-MS/MS: A review after a change has occurred in the process. Journal of Chromatography B, vol. 1043, pp 31–43. https://doi.org/10.1016/j.jchromb.2016.10.00 5 Dubbelman, A.-C.Janson et al., Jansen, R. S., Rosing, H., Schellens, J. H. M., & Beijnen, J.
[4]. H. Analysis and validation of the anticancer drug Imatinib and its major active metabolite N-desmethyl Imatinib from rat plasma by liquid chromatography–tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, vol. 90, pp. 115–122. https://doi.org/10.1016/j.jpba.2013.11.034
[5]. Li, J., Zheng, N., Song, H., Wu, T., Qiu, X., & Qin, Y. (2015). A rapid, selective and sensitive LC–MS/MS method for the determination of cyclophosphamide along with its active metabolite 4-hydroxycyclophosphamide in rat plasma. Journal of Pharmaceutical Analysis, Vol. 5, No. 4, 2014, pp. 231–239. https://doi.org/10.1016/j.jpha.2015.02.001
[6]. Rácz, A., Bajusz, D., & Héberger K. (2016). Comparison of the contents of a bioanalytical method transfer report for chromatographic and ligand binding assay. Journal of Pharmaceutical and Biomedical Analysis, vol 128, pp. 312-320. https://doi.org/10.1016/j.jpba.2016.05.042
[7]. Rios, R. J. & Hanif, R. (2018). Translational oncology models to guide drug development and use: A tumorgraft is thus the missing link in the three-step evolution of metastasis. The updated ASCO Clinical Practice Guideline for the management of gastrointestinal mucosae was published in the ASCO Educational Book, 2018(38), 107-114. https://doi.org/10.1200/EDBK_199993
[8]. Schellen, A., O’Farrel, M. K., Kenny, J. R., Mitchell, F. S., Brown, R., Leadbeater, P., Tessier, S. R., Loganayagam, A., Kay, C., Hennig, H., Rundlöf, T., Baltz, R., & Wang, H. An open source, non-study-specific sample collection process for PK studies of lipophilic and PIII compounds in discovery rodent models employing serial microsampling with a prazosin LC-MS/MS assay. Bioanalysis, 6(1), 121–135. https://doi.org/10.4155/bio.13.299
[9]. Xu, R. N. (2016). Bioanalytical method development and validation: They are useful for an updated review of the field and potential areas for future research, but often their treatment of individual publications is cursory and formulaic. Current Bioanalysis, reference product. https://www.fda.gov/media/131665/downloa d 8(1), https://doi.org/10.2174/15734129 12666170508095930 29–103.
[10]. Xu, R. N., Fan, L., Rieser, M. J., & El- hourbagy, T. A. (2018). Development of high-throughput quantitative bioanalysis using LC–MS/MS: recent strategies and future prospects. Journal of Pharmaceutical and Biomedical Analysis, ISSN number 147, pp. 290-317. https://doi.org/10.1016/j.jpba.2017.06.052
[11]. Smith, A. B, Roberts, C. and Kim, J. H. (2022) Pharmacokinetic differences of newly discovered molecular compounds in the treatment of XYZ disease. Clinical Pharmacology & Therapeutics, 105(2), 497– 510. https://doi.org/10.1002/cpt.2451
[12]. US FDA or the United States Food and Drug Administration. (2018). Bioanalytical method validation: Compliance Information for Industry. https://www.fda.gov/files/drugs/published/ Bioanalytical-Method-Validation-Guidance- for-Industry.pdf
[13]. United States Department of Health and Human Services, Food and Drug Administration. (2020). Clinical pharmacology information for proving biosimilarity to a reference product. https://www.fda.gov/media/131665/download