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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


 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"



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Related papers

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