Simultaneous Quantitative Estimation of Lisinopril and Hydrochlorothiazide Residues and Establishing Cross-Contamination Limits for Cleaning Validation

Imeda Rubashvili, #14 Chirnalkhuli Street, Pharmaceutical Company “Aversi-Rational” Ltd., Tbilisi, Georgia, Tbilisi, Georgia (rubashvili@yahoo.fr)

Cleaning validation is a critical process of quality assurance system including the development and validation of sampling procedures of active pharmaceutical ingredients residues on pharmaceutical equipment surfaces, the establishing  allowable limits  and quantitative determination of the above-mentioned residues in the collected samples from surfaces.

The aim of this study was to validate direct - swab and indirect - rinse sampling procedures and demonstrate the applicability of developed HPLC method for simultaneous quantitative estimation of residues of active pharmaceutical ingredients – lisinopril and hydrochlorothiazide in cleaning control samples collected from pharmaceutical equipment surfaces after manufacturing of lisinopril/hydrochlorothiazide 20/25 mg uncoated tablets. The swab and rinse sampling procedures were developed in order to obtain a suitable and good recovery (>80 %). The sampling procedures were qualified. The influence of swab material on quantitative determination of lisinopril and hydrochlorothiazide were checked as well.

It has been shown the methodology of establishing  the allowable limits of the above-mentioned APIs on the manufacturing equipment surfaces which were based on pharmacological and toxicological criteria.

The method for simultaneous quantitative determination of lisinopril and hydrochlorothiazide residues was developed using LC system “Ag 1260 Infinity” and BDS Hypersil C8 250 × 4.0 mm, 5 µm column with isocratic elution. The method was validated with respect to robustness, system suitability test, specificity, linearity-range, accuracy, precision (intra-day and inter day), limit of detection (LOD) and quantitation (LOQ). The stability of solutions and 0.45 µm membrane filter compatibility were studied as well. These studies were performed in accordance with established ICH Q2 guideline and USP requirements. The calibration curves are linear (r² =1.00000) over a wide concentration range 0.155 – 10.0 µg/mL for lisinopril and 0.025 – 12.5 µg/mL for hydrochlorothyazide; the LOD and LOQ for lisinopril  - 0.039 µg/mL and 0.155 µg/mL, for hydrochlorothyazide - 0.012 µg/mL and 0.025 µg/mL, respectively.

---

Short Biography of Presenting Author

Imeda Rubashvili has completed his PhD at the age of 26 years from Georgian Technical University. He is a senior scientific researcher at Ivane Javakhishvili Tbilisi State University and the head of validation department of pharmaceutical company “Aversi-Rational” Ltd. He has published more than 30 scientific papers in peer-reviewed journals. He is the member of the council of young scientists of the Georgian National Academy of Sciences.