Analysis of five HMG-CoA reductase inhibitors-- atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin: pharmacological, pharmacokinetic and analytical overview and development of a new method for use in pharmaceutical formulations analysis and in vitro metabolism studies.
A specific, accurate, precise and reproducible high-performance liquid chromatographic (HPLC) method was developed and validated for the simultaneous quantitation of five 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, viz. atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin, in pharmaceutical formulations and extended the application to in vitro metabolism studies of these statins. Ternary gradient elution at a flow rate of 1 mL/min was employed on an Intertisl ODS 3V column (4.6 x 250 mm, 5 microm) at ambient temperature. The mobile phase consisted of 0.01 m ammonium acetate (pH 5.0), acetonitrile and methanol. Theophylline was used as an internal standard (IS). The HMG-CoA reductase inhibitors and their metabolites were monitored at a wavelength of 237 nm. Drugs were found to be 89.6-105.6% of their label's claim in the pharmaceutical formulations. For in vitro metabolism studies the reaction mixtures were extracted with simple liquid-liquid extraction using ethyl acetate. Baseline separation of statins and their metabolites along with IS free from endogenous interferences was achieved. Nominal retention times of IS, atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin were 7.5, 17.2, 21.6, 28.5, 33.5 and 35.5 min, respectively. The proposed method is simple, selective and could be applicable for routine analysis of HMG-CoA reductase inhibitors in pharmaceutical preparations as well as in vitro metabolism studies.
Pasha
Md Khalid
MK
Drug Metabolism and Pharmacokinetics, Discovery Research, Dr. Reddy's Laboratories Ltd, Miyapur, Hyderabad, India.
Muzeeb
Syed
S
Basha
Shaik Jafar Sadik
SJ
Shashikumar
Dhanya
D
Mullangi
Ramesh
R
Srinivas
Nuggehally R
NR
D000818:Animals; D000069059:Atorvastatin; D002851:Chromatography, High Pressure Liquid; D005464:Fluorobenzenes / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006538:Heptanoic Acids / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008148:Lovastatin / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D017035:Pravastatin / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D011743:Pyrimidines / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D011758:Pyrroles / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D013449:Sulfonamides / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology
D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D004364:Pharmaceutical Preparations; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin