Development and validation of the HPLC-UV method for impurities determination in duloxetine hydrochloride

Anna Rosa ,  Ewelina Czerniec-Michalik ,  Maria Puchalska ,  Joanna Zagrodzka ,  Iwona Bujak ,  Damian Kowalski ,  Zbigniew Araźny ,  Wojciech Łuniewski 

Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland

Abstract

 Duloxetine hydrochloride (DX) [(+)-(S)-N-Methyl- 3-(naphthalen-1-yloxy)-3-(thiophen-2-yl) ] propan-1-amine hydrochloride] is an antidepressive drug effective for mood disorders and also the stress urinary incontinence. Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI). The serotonin and norepinephrine are neurotransmitters responsible for connection between nerve cells. Besides effectiveness in treatment of mental disorders these hormones are involved in process of pain reduction. Duloxetine increases the level of neurotransmitters in the brain, which affect course of anxiety, diabetic neuropathic pain and attention deficit hyperactivity disorder (ADHD).   

                                                 
                               duloxetine (DX)                            DX isomer

Reversed phase liquid chromatography (RP - HPLC)  as an analytical technique was used  to control the synthesis route and for the determination of impurities of duloxetine hydrochloride. Resolution between potential contaminants and by-products of DX is based on the difference in polarity. One of potential impurities determined in duloxetine samples is DX isomer described in pharmacopoeia monograph [1]. During the method development it was found that the separation between DX and its isomer is the critical point of the HPLC method. The value of resolution (RS) should be higher than 1.5.
The final HPLC method does not require ion-pair and buffer use in contrast to methodologies described in available analytical literature [1,2].

The chromatographic separation was achieved on a C-18 column using gradient elution and the mixture of water, methanol, tetrahydrofuran with the addition of trifluoroacetic acid as the mobile phase. Analysis were performed at 230 nm [2].

The validation of the HPLC method included: specificity and selectivity studies, determination of linearity, limits of detection (LOD) and quantification (LOQ), accuracy, repeatability and robustness [3,4].

[1] European Pharmacopoeia for Duloxetine hydrochloride (p.2594)

[2] Estimation of duloxetine hydrochloride in pharmaceutical formulations by RP-HPLC method, Sejal K. Patel, N.J. Patel, K.M. Patel, P.U. Patel,B.H.Patel, S.K. Patel, Ganpat UniversityKherava-382 711, India

[3] A validated stability indicating rapid LC method for duloxetine HCl, Srinivasulu P.,Srinivas K.S., Reddy RS, Mukkanti K., Buchireddy R., Inogent Laboratories  Pvt. Ltd., Hyderabad, India

[4] International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonized Tripartite Guideline "Q2B: Validation of Analytical Procedures: Methodology; Availability," "Q2A: Text on Validation of Analytical Procedures"

 

 

Related papers
  1. The comparison of the stability indicating  two HPLC methods and their application for the determination of bosentan in coated tablets 
  2. Determination of organic volatile impurities in Nepafenac by GC method
  3. Application of the new data processing method for photodiode array detector in the analysis of drug substances
  4. Improved manufacturing process of bosentan monohydrate.
  5. Development and validation of the GC method for quantitative determination of semi-volatile solvents in pharmaceutical substance Bosentan
  6. Validation of HPLC methods for analyzing the chemical purity of cilostazol
  7. Identification of degradation products of cilostazol drug substance
  8. An application of accelerator mass spectrometry (AMS) in pediatric clinical studies. Paracetamol, midazolam and spironolactone radiosynthesis and certification.
  9. Assessment of selected synthesis of bosentan towards elimination of known impurities.
  10. Comparative permeation studies of tacalcitol through the human skin from brand product versus generic product
  11. HPLC methods for in–process control and chemical purity determination of olopatadine
  12. Development and validation of HPLC method. Review of selected cases.
  13. HPLC method for determination of the enantiomeric purity of a new ω chain aldehyde synthon used in the synthesis of travoprost
  14. Synthesis and biological evaluation of new amino acid and dipeptide derivatives of neocryptolepine as anticancer agents. 
  15. Analytical control of synthesis and determination of BR-S by HPLC
  16. Optimization of BR-8 synthesis
  17. Opimisation of preparation of TZ-6
  18. HPLC method as an analitycal control of synthesis and determination of TZ-S
  19. The synthesis of ezetimibe with high stereochemical purity
  20. Investigation of unknown impurity of TD-S by HPLC-MS
  21. Validation of a HPLC method for LI-S analysis
  22. HPLC Methods for Stress Testing of ZL-S Drug Substances
  23. The evaluation of tolterodine tartrate synthesis based on patent EP 0 325 574 B1.
  24. Zolmitriptan synthesis and in-process control by HPLC methods
  25. Disubstituted indolo[2,3-b]quinoline derivatives - the cytotoxic activity in vitro against various human tumor cell lines.
  26. Mono substituted 5H- and 6H-indolo[2,3-b]quinoline derivatives and their ability to overcome the barrier of drug resistance.
  27. Synthesis of selected 14C radiolabelled compounds in recent investigations of new analytical method applied in accelerated drug development (EUMAPP).
  28. HPLC as a method for analytical control of synthesis and determination of tolterodine (TD-S)
  29. Development of HPLC and GC methods for analysis of Zolmitriptan of pharmaceutical purity
  30. QUINONES AND HYDROQUINONES SEPARATION AND DETERMINATION BY HPLC CHROMATOGRAPHY
  31. HPLC AS A METHOD FOR ANALYTICAL CONTROL OF SYNTHESIS AND DETERMINATION OF PRAMIPEXOLE
  32. MONO SUBSTITUTED 5H-INDOLO[2,3-B]- QUINOLINE DERIVATIVES AND THEIR ABILITY TO OVERCOME THE BARRIER OF DRUG RESISTANCE.
  33. DISUBSTITUTED INDOLO[2,3-b]QUINOLINE DERIVATIVES. THE CYTOTOXIC ACTIVITY IN VITRO AGAINST VARIOUS HUMAN TUMOR CELL LINE.
  34. NEW IMPROVED METHOD OF POLYMORPHIC α FORM OF IMATINIB MESYLATE (GLEEVEC®) SYNTHESIS.

Presentation: Poster at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Anna Rosa
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2012-03-27 16:55
Revised:   2012-05-11 01:55