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Stress Studies and Identification of Degradation Products of Cephalexin Using LC–PDA and LC–MS/MS

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Abstract

A stability indicating RP-HPLC method for cephalexin has been developed and validated to identify and characterize potential degradation products. Drug was subjected to hydrolytic (acidic, basic, and neutral), oxidative, thermal, and photolytic stresses as per ICH guidelines Q1A (R2) and Q1B. Chromatographic separation was achieved on C8 column with mixture of ammonium acetate buffer pH 4.5 and acetonitrile in gradient mode as a mobile phase with PDA detection. Specificity of the method was established by peak purity studies. Method was validated as per ICH guideline Q2 (R1) for accuracy, precision, linearity, sensitivity, and robustness. Kinetics for each degradation condition was studied with respect to order of reaction and rate constant. Method was found to comply with acceptance criteria of validation parameters with respect to specificity (peak purity greater than 0.999) linearity (r 2 greater than 0.99), accuracy (% recovery in the range of 98–102%), and precision (% RSD not more than 2). A total of six degradation products were generated in different stress conditions; these were identified and structures were proposed using LC–MS/MS. Cephalexin undergoes degradation in almost all the conditions. The developed stability indicating method is suitable for analysis of stability samples as it adequately separates all degradation products. Degradation products generated in photolytic and oxidative conditions are reported for the first time.

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Abbreviations

BP:

British Pharmacopoeia

CPL:

Cephalexin

ICH:

International conference of harmonization

IP:

Indian Pharmacopoeia

LC–MS:

Liquid chromatography–mass spectrometry

PDA:

Photodiode array

RP-HPLC:

Reversed-phase high-performance liquid chromatography

RSD:

Relative standard deviation

SIAM:

Stability indicating analytical method

TOF:

Time of flight

USP:

United States Pharmacopoeia

UV:

Ultraviolet

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Acknowledgements

Authors are thankful to Sinhgad College of Pharmacy Vadgaon, (Bk.) Pune and Sophisticated Analytical Instrument Facility, IIT, Bombay for providing necessary facilities to carry out the work.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, STES’s Sinhgad Institute of Pharmacy, Off Smt. Kashibai Navale Hospital, Narhe Road, Near Bank of Maharashtra, Narhe, Pune, Maharashtra, 411041, India

    V. T. Gawande, K. G. Bothara & A. M. Marathe

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  1. V. T. Gawande
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  2. K. G. Bothara
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  3. A. M. Marathe
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Correspondence to V. T. Gawande.

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Gawande, V.T., Bothara, K.G. & Marathe, A.M. Stress Studies and Identification of Degradation Products of Cephalexin Using LC–PDA and LC–MS/MS. Chromatographia 80, 1545–1552 (2017). https://doi.org/10.1007/s10337-017-3385-0

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