Development and Validation of Rapid Resolution RP-HPLC Method for Simultaneous Determination of Atorvastatin and Related Compounds by Use of Chemometrics

Abstract

A Rapid Resolution Reversed Phase High-Performance Liquid Chromatography (RR RP-HPLC) method has been developed and validated for the simultaneous determination of atorvastatin and seven related compounds specified as impurities. Experimental design was used during method optimization (full factorial 3² design) and robustness testing (central composite design). Chromatography was performed with mobile phase containing phosphate buffer pH 3.5 and a mixture of 10% (v/v) tetrahydrofuran in acetonitrile as organic modifier. A Zorbax Eclipse XDB C18 Rapid Resolution HT 4.6 mm × 50 mm, 1.8 µm particle size column was used. The developed method allowed determination of Atorvastatin Calcium (ATV Ca) purity and level of impurities in drug substances.

Keywords:

• Atorvastatin
• Experimental design
• Impurities
• Rapid Resolution RP-HPLC
• Validation

Notes

∗Eluted peak pairs refer to the text.

∗∗Organic phase variation during gradient elution.

t _r  = retention time, k = capacity factor, ∗Eluted peaks: (1) ATV eliminate, (2) desfluoro ATV, (3) trans ATV, (4) ATV Ca, (5) diamino ATV, (5) ATV lactone, (7) ATV dihydroxy, (8) ATV diketone.

∗Eluted peak pairs refer to the text.

∗Eluted peaks: (1) ATV eliminate, (2) desfluoro ATV, (3) trans ATV, (4) ATV Ca, (5) diamino ATV, (6) ATV lactone, (7) ATV dihydroxy, (8) ATV diketone, a = intercept, b = slope, Sa = standard deviation of the intercept, Sb = standard deviation of the slope, R ²  = coefficient of correlation, LOD = limit of detection, LOQ = limit of quantification.

∗Impurities: (1) ATV eliminate, (2) desfluoro ATV, (3) trans ATV, (4) diamino ATV, (5) ATV lactone, (6) ATV dihydroxy, (7) ATV diketone, ∗∗S = standard deviation (n = 5).

∗Eluted peak pairs refer to the text.

∗Eluted peak pairs refer to the text.