Lean Six Sigma–Driven Development and Validation of a Robust RP-HPLC Method for Simultaneous Estimation of Dapagliflozin and Linagliptin in Tablet Dosage Form

Abstract

Robust analytical methods are essential for pharmaceutical quality and regulatory compliance. This study
developed a reversed-phase HPLC method for simultaneous quantification of Dapagliflozin and
Linagliptin in tablets, integrating Lean Six Sigma (DMAIC) principles to enhance reliability and
efficiency. Chromatographic separation used an Inertsil C18 column (250 × 4.6 mm, 5 μm) with
phosphate buffer (pH 3) and methanol (70:30, v/v) at 1.0 mL/min, detecting at 260 nm. Retention times
were 2.669 min for Dapagliflozin and 3.855 min for Linagliptin. The method showed excellent linearity
(r² > 0.999) across 10–50 μg/mL and 5–25 μg/mL ranges, respectively. Validation per ICH Q2(R1)
confirmed specificity (no excipient interference), accuracy (99.84–100.51% recovery), precision (RSD <
1.5%), LOD (0.08–0.12 μg/mL), LOQ (0.24–0.36 μg/mL), and robustness (<1.5% peak area variation
with ±2% mobile phase change). Resolution reached 5.27 with >12,000 theoretical plates for both
analytes. DMAIC integration enabled systematic target definition, variability reduction, critical
parameter identification, and 35% solvent waste reduction. Development time decreased by 28% while
maintaining sustained performance through control charts. This validated method offers a reliable,
efficient tool for routine quality control, supporting regulatory expectations for robustness and sustainable
laboratory practices.