Quantification of Genotoxic Impurities in Key Starting Material of Sertraline Hydrochloride by Simple and Sensitive Liquid Chromatography Technique

Author(s): Ajit Anerao*, Vishal Solase, Thaksen Gadhave, Amol More, Nitin Pradhan.

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 1 , 2020

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Abstract:

Background: Schiff base is an advanced key starting material of Sertraline hydrochloride. Schiff base is synthesized using two raw materials 1-Naphthol and 1,2-Dichlorobenzene which are potentially genotoxic impurities.

Objective: Genotoxic impurities need to be controlled in key starting material to avoid carry forward in the active pharmaceutical ingredient. For trace level quantification of impurities a sensitive, accurate and cost effective method is developed by simultaneous estimation of both impurities.

Methods: Reverse phase high performance liquid chromatography (HPLC) method was developed and validated for determination of both impurities in Schiff base. HPLC column Cosmosil MS-II C18, 100 mm X 4.6 mm, 3 μm particle size with ultra-violet detector (UV) was used.

Results: The calibration curve of 1-Naphthol and 1,2-Dichlorobenzene showed good linearity over the concentration range of 0.25 µg/g to 7.5 µg/g and 1.5 µg/g to 7.5 µg/g and the regression coefficient was 0.999 and 0.998 respectively. Method had very low limit of detection (LOD) and limit of quantification (LOQ) of both analytes which proves that the method is sensitive and suitable for quantification of compounds at trace level.

Conclusion: The proposed method is specific, linear, accurate, rugged and precise. Genotoxic impurities 1-Naphthol and 1,2-Dichlorobenzene are quantified and controlled in the key starting material of Sertraline hydrochloride. The validated method can be used in quality control unit in pharmaceutical industry.

Keywords: Sertraline, genotoxic, impurity, method development, validation, liquid chromatography.

[1]
Veerle, G.; Katleen, V.S.; Damiaan, D.; Dieter, D. Selective serotonin reuptake inhibitors as a novel class of immunosuppressants. Int. Immunopharmacol., 2014, 20(1), 148-156.
[2]
Janet, E.A.; Linda, E.L.; Patricia, A.B.; Kristan, J.A. Selective serotonin reuptake inhibitor (SSRI) antidepressants, prolactin and breast cancer. Front. Oncol., 2012, 2, 1-9.
[3]
Pohl, R.B.; Wolkow, R.M.; Clary, C.M. Sertraline in the treatment of panic disorder. A double-blind multicenter trial. Am. J. Psychiatry, 1998, 155, 1189-1195.
[4]
Katzelnick, D.J.; Kobak, K.A.; Greist, J.H.; Jefferson, J.W.; Mantle, J.M.; Serlin, R.C. Sertraline for social phobia: a double-blind, placebo-controlled, crossover study. Am. J. Psychiatry, 1995, 152, 1368-1371.
[5]
Greist, J.H.; Jefferson, J.W.; Kobak, K.A. A one-year, double-blind, placebo-controlled fixed dose study of sertraline in the treatment of obsessive-compulsive disorder. Int. Clin. Psychopharmacol., 1995, 10, 57-65.
[6]
Jeffrey, V.; Amir, H.K. Generic penetration in the retail antidepressant market. Psychiatry, 2010, 7(6), 9-11.
[7]
The United State Pharmacopoeia 39; sertraline hydrochloride monograph; 2016, 3, 5831-5833.
[8]
European pharmacopoeia 8.0; sertraline hydrochloride monograph; 1705, 2011, 3, 3210-3212.
[9]
Krisztina, V.; Tama, F.; Ja’nos, F.; Ire’n, F.; Sa’ndor, L. Improved industrial synthesis of antidepressant sertraline. Org. Process Res. & Dev., 2002, 6, 82-85.
[10]
Dichlorobenzenes; Agency for Toxic Substances and Disease Registry; ATSDR – Tox. Sub.; 2018; Available at: https://www.atsdr.cdc.gov/substances/toxsubstance.asp?toxid=126 (Accessed on: January 10, 2018).
[11]
,2-Dichlorobenzene; Integrated Risk Information System (IRIS); U.S. Environmental Protection Agency; Chemical Assessment Summary; Nat. Cen. for Env. Ass.; Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/subst/0408_summary.pdf (Accessed on: May 01, 2015).
[12]
Mete, K.; Zeynep, U.; Sezin, G.; Lokman, A. Determination of cytotoxic and genotoxic effects of naphthalene, 1-naphthol and 2-naphthol on human lymphocyte culture. Tox. Ind. Health, 2014, 30(1), 82-89.
[13]
ICH; M7 (R1) Addendum to ICH M7; Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk; Application of the Principles of the ICH M7 Guidance to Calculation of Compound-Specific Acceptable Intakes; ICH Harmon. Guide;> 2015.
[14]
ICH; Impurities in new drug substances Q3A (R2); 2006.
[15]
FDA; U.S. Dept of Health and Human Services Food and Drug Adm. Guidance for Industry ANDAs; Impurities in Drug Substances; 2009.
[16]
Rxlist; Zoloft; Available at: https://www.rxlist.com/zoloft-drug.htm#indications_dosage (Accessed on: January 03, 2017).
[17]
Sertraline dosage; Available at: https://www.drugs.com/dosage/sertraline.html (Accessed on: May 01, 2017).
[18]
Naphthalene metabolites 1-naphthol and 2-naphthol; The MAKCollection for Occupational Health and Safety; Part IV: Bio-mon. Met.; 2007; 12; Available at: https://onlinelibrary.wiley.com/ doi/pdf/10.1002/3527600418.bi9015e0012b (Accessed on: March 20, 2015).
[19]
Ralf, P.; Jürgen, A. Simultaneous determination of 1- and 2-naphthol in human urine using on-line clean-up column-switching liquid chromatography-fluorescence detection. J. Chrom. B, 2004, 801(2), 307-316.
[20]
Sancho, J.; Cabanes, R.; López, F. Hernández, F. Direct determination of 1-naphthol in human urine by coupled-column liquid chromatography with fluorescence detection. Chromatographia, 2003, 58(9-10), 565-569.
[21]
Chlorobenzenes; Bio-mon. Met., 1982; 1; Available at: https://onlinelibrary.wiley.com/doi/pdf/10.1002/3527600418.bi9550dtre0001 (Accessed on: March 20, 2015).
[22]
Wolska, L.; Konieczka, P.; Jastrzebska, A.; Namiesnik, J. Analytical procedure for the determination of chlorobenzenes in sediments. J. Chrom. Sci., 2003, 41, 53-56.
[23]
Cheri, C.; Burke, M.; LeMoine, E. U.S. EPA Volatile Organics Method 524.2 using purge and trap GC/MS; Environmental Application Notes; PerkinElmer Inst.; 2000. Available at: https://www.perkinelmer.com/content/applicationnotes/app_usepa5242volatileorganics.pdf
[24]
Jandera, P.; Fischer, J.; Prokeš, B. HPLC determination of chlorobenzenes, benzenesulphonyl chlorides and benzenesulphonic acids in industrial waste water. Chromatographia, 2001, 54(9-10), 581-587.
[25]
Zhiming, Y.; Wenmin, Z.; Jia, G.; Yifen, L.; Jianrong, L.; Zian, L.; Lan, Z. Reverse-phase high performance liquid chromatography separation of positional isomers on the MIL-53(Fe) packed column; Rsc. Adv, 2015, pp. 40094-40102.
[26]
ICH; Validation of analytical procedures: Text and methodology Q2 (R1); 2005.


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Article Details

VOLUME: 16
ISSUE: 1
Year: 2020
Page: [110 - 116]
Pages: 7
DOI: 10.2174/1573412914666180716160507

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