Development and Application of a Validated HPLC Method for the Determination of Clindamycin Palmitate Hydrochloride in Marketed Drug Products: An Optimization of the Current USP Methodology for Assay

Geoffrey K. Wu, Abhay Gupta, Mansoor A. Khan, Patrick J. Faustino

Division of Product Quality Research, Office of Pharmaceutical Science, Food and Drug Administration, Silver Spring, USA..
ivision of Product Quality Research, Office of Pharmaceutical Science, Food and Drug Administration, Silver Spring, USA..
Office of Generic Drugs, Food and Drug Administration, Rockville, USA.

DOI: 10.4236/jasmi.2013.34026                

Abstract

A simple efficient isocratic reversed-phase HPLC method was developed and validated for the determination of clindamycin palmitate hydrochloride (CPH) and its commercially available oral solution products. Separation was achieved on a Phenomenex Zorbax (Luna) cyano column (150 × 4.6 mm, 5 μm) with a Phenomenex cyano guard cartridge (4 × 3.0 mm) on Agilent 1050 series HPLC system. CPH and its resolution standard lincomycin were eluted isocratically at a flow rate of 1 mL/min with a simplified mobile phase (potassium phosphate buffer (5 mM, pH 3.0)—acetonitrile—tetrahydrofuran (20:75:5, v/v/v)) and detected at 210 nm. The column was maintained at 25?C. The method was validated according to USP category I requirements. Robustness and forced degradation studies were also conducted. CPH marketed drug products were obtained from a drug distributor and assayed for potency using the validated method. Validation acceptance criteria were met in all cases. The analytical range for CPH was 15 - 500 μg/mL and the linearity was r² > 0.999 over three days. The method was determined to be specific and robust. Both accuracy (92.0% - 103.8%) and precision (0.67% - 1.52%) were established across the analytical range for low, intermediate and high QC concentrations. Method applicability was demonstrated by analyzing two marketed products of CPH, in which results showed potency >98%. The method was determined to be an enhancement over the current USP methodology for assay as a result of increased efficiency, reduced organic solvents and the elimination of matrix modifiers. This method was successfully applied for the quality assessment of: 1) currently marketed drug products and 2) will in future assess the product quality of novel dosage forms of CPH for pediatric use.

Keywords

Clindamycin Palmitate Hydrochloride (CPH); HPLC; Method Validation; Pediatric Dosage Form

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	A. A. Forist, R. M. DeHaan and C. M. Metzler, “Clindamycin Bioavailability from Clindamycin-2-Palmitate and Clindamycin-2-Hexadecylcarbonate in Man,” Journal of Pharmacokinetics and Biopharmaceutics, Vol. 1, No. 2, 1973, pp. 89-98. http://dx.doi.org/10.1007/BF01059623
[2]	M. Cimbollek, N. Nies, A. Liebendorfer, et al., “The Potential of the Prodrug Clindamycin Palmitate as an Implantable Slow Release form of the Antibotic Clindamycin for Heart Valves,” Journal of Controlled Release, Vol. 33, No. 1, 1995, pp. 47-53. http://dx.doi.org/10.1016/0168-3659(94)00061-X
[3]	United States Pharmacopeia, “Clindamycin Palmitate Hydrochloride,” United States Pharmacopeia (36) and National Formulary (31), 2013, pp. 3028-3029.
[4]	L. W. Brown, “High-Pressure Liquid Chromatographic Assays for Clindamycin, Clindamycin Phosphate, and Clindamycin Palmitate,” Journal of Pharmaceutical Sciences, Vol. 67, No. 9, 1978, pp. 1254-1257. http://dx.doi.org/10.1002/jps.2600670917
[5]	C. Bharathi, P. Jayaram, J. S. Raj, et al., “Identification, Isolation and Characterization of Impurities of Clindamycin Palmitate Hydrochloride,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 48, No. 4, 2008, pp. 1211-1218. http://dx.doi.org/10.1016/j.jpba.2008.08.011
[6]	C. B. V. N. Raju, G. Panda, G. N. Rao, et al., “HPLC-UV Assay Method for Clindamycin Palmitate Hydrochloride as Drug Substance and Oral Solution,” Analytical Letters, Vol. 41, No. 11, 2008, pp. 2033-2043. http://dx.doi.org/10.1080/00032710802209334
[7]	E. L. Rowe, “Anomalous Solution Behavior of 2-Pal-mitate Esters of Lincomycin and Clindamycin,” Journal of Pharmaceutical Sciences, Vol. 68, No. 10, 1979, pp. 1292-1296. http://dx.doi.org/10.1002/jps.2600681025
[8]	L. W. Brown and W.F. Beyer, “Clindamycin Hydrochloride,” In: K. Florey and G. Rafik Bishara, Ed., Analytical Profiles of Drug Substances, Acedemic Press, Inc., London, 1981, pp. 75-91.
[9]	S. M. Wang, S. S. Bu, H. M. Liu, et al., “Separation and Characterization of Clindamycin Phosphate and Related Impurities in Injection by Liquid Chromatography/Electrospray Ionization Mass Spectrometry,” Rapid Communications in Mass Spectrometry, Vol. 23, No. 6, 2009, pp. 899-906. http://dx.doi.org/10.1002/rcm.3935
[10]	United States Pharmacopeia, “General Information <1225> Validation of Compendial Procedures,” United States Pharmacopeia (36) and National Formulary (31), 2013, pp 983-988.
[11]	“Guidance for Industry Q2B Validation of Analytical Procedures: Methodology,” International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), 1996.
[12]	United States Pharmacopeia, “Materials Safety Data Sheet: Clindamycin Palmitate Hydrochloride,” 2007. http://www.usp.org/pdf/EN/referenceStandards/msds/1137005.pdf
[13]	B. Dejaegher and Y.V. Heyden, “Ruggedness and Robustness Testing,” Journal of Chromatography A, Vol. 1158, No. 1-2, 2007, pp. 138-157. http://dx.doi.org/10.1016/j.chroma.2007.02.086
[14]	M. Bakshi and S. Singh, “Development of Validated Stability-Indicating Assay Methods—Critical Review,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 28, No. 6, 2002, pp. 1011-1040. http://dx.doi.org/10.1016/S0731-7085(02)00047-X