Atorvastatin calcium: Chemical property, Spectroscopy, and Side effects

Introduction

Atorvastatin calcium (LIPITOR ) is [R-(R*, R*)]-2-(4-fluorophenyl)-β, δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1Hpyrrole-1-heptanoic acid, calcium salt (2:1)trihydrate. The empirical formula of atorvastatin calcium is(C33H34FN2O5)2Ca•3H2O, and its molecular weight is 1209.42.

Chemical property

Atorvastatin calcium is a white to off-white crystalline powder that is insoluble in aqueous solutions of pH 4 and below. Atorvastatin calcium is slightly soluble in distilled water, pH 7.4 phosphate buffer, and acetonitrile; slightly soluble in ethanol; and freely soluble in methanol.

LIPITOR Tablets for oral administration contain 10, 20, 40, or 80 mg of atorvastatin and the following inactive ingredients: calcium carbonate, USP; candelilla wax, FCC; croscarmellose sodium, NF; hydroxypropyl cellulose, NF; lactose monohydrate, NF; magnesium stearate, NF; microcrystalline cellulose, NF; Opadry White YS-1-7040(hypromellose, polyethylene glycol, talc, titanium dioxide); polysorbate 80, NF; simethicone emulsion.

Spectroscopy

Atorvastatin calcium was dissolved in methanol at a concentration of 4 μg/ml, and the resulting UV absorption spectrum is shown below. The analytically useful wavelength maximum (λmax) of atorvastatin calcium in methanol is approximately 246 nm.

The Nuclear magnetic resonance (NMR) spectra of atorvastatin were assigned according to the following numbering system. The first figure is the 1H NMR spectrum of atorvastatin calcium, and the second one is an Assignment for the resonance bands in the 1H NMR spectrum of atorvastatin calcium (solvent: CH3OH-d3).

Mechanism of Action

LIPITOR is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3­ methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. In animal models, LIPITOR lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell surface to enhance uptake and catabolism of LDL; LIPITOR also reduces LDL production and the number of LDL particles.

Side effects

Serious side effects

Talk to a doctor if you notice any signs or symptoms of a possible serious side effect, including:

Unexplained muscle pain, tenderness, or weakness

Change in how much or how often you urinate.

Dark urine or pale stools, nausea, vomiting, loss of appetite, stomach pain, yellow skin or eyes

Unusual tiredness

Fever

Blistering, peeling, red skin rash

Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing

Less serious side effects of atorvastatin:

Runny nose, stuffy nose, sore throat

Joint pain

Diarrhea

Pain in the arms, legs, hands, or feet