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Stability Indicating Method Development and Validation for Hydrocodone Degradants in Ibuprofen Hydrocodone (200mg/7.5mg) Tablets

H. Chen 1, C. Chan 1, B. V. Osdel 1, I. Gibson 1 1 Nexgen Pharma Purpose. A stability-indicating method was needed to quantify Hydrocodone-specific degradants, limited to 0.2% of the Hydrocodone API, as well as the known degradant, Hydrocodone N-Oxide (HCNO), limited to 0.5%. Methods. Two HPLC method approaches were tried: 1) Reverse phase C18 column 150x4.6 mm, 1.5 mL/min, 95% 20mM pH2.8 Phosphate Buffer/5% ACN; and 2). Ion exchange SCX column 150x4.6 mm, 1.5 mL/min, 57% 25mM pH 2.2 Phosphate Buffer/43% ACN. For both approaches, the respective buffer alone was used as the sample preparation diluent. Results. 1. The PDA spectra of observed peaks showed that no trace of Ibuprofen or its known degradants made it into the chromatography. Ibuprofen and its degradants were practically insoluble in 100% aqueous pH 2.2-2.8 buffered diluent. 2. Although the reverse phase did separate four unknown degradants from Hydrocodone, HCNO eluted entirely within the Hydrocodone peak. 3. Ion exchange not only resolved HCNO, but also two additional unknowns (total six) not separated out by the C18 method. The target analytes had greater variation in charge than hydrophobicity. 4. A full validation was completed by using the ion exchange method. a. The LOQ for Hydrocodone and HCNO were both 0.075% of the API. b. Linearity Hydrocodone and HCNO both had a correlation coefficient of 1.000 from 0.075% to 2.0% of the API. c. Recovery of HCNO at 0.25%, 0.50% and 1.0% of the API was within 90-110%. d. The method precision was 1.8% RSD. e. The method passed all criteria for a full stress study under light, heat, humidity, acid/base hydrolysis and oxidation. f. Other validation parameters had also been performed: relative response factor, ruggedness, robustness, and solution stability. Conclusion. Choosing the 100% aqueous, acid-buffered diluents eliminates the interference from 200 mg of the Ibuprofen and its related substances prior to the chromatography. The stability indicating HPLC method using the ion exchange column for related substances of Hydrocodone in Ibuprofen Hydrocodone Tablets (200mg/7.5mg) was successfully validated and used for routine analysis.

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Microsoft Word - PSWC2010-001142.doc