Development and validation of a chiral liquid chromatographic method for the determination of atenolol and metoprolol enantiomers in tablet preparations.

Atenolol (AT) and metoprolol (MT) are predominantly used in the treatment of angina pectoris, certain arrhythmias, systemic hypertension, and several other cardiovascular disorders. Both compounds are produced commercially in the racemic form, although the S-form is responsible for the desired biological effect. This paper describes a simple, rapid, precise, and accurate method for separating the enantiomers of AT and MT. AT isomers are separated by using a Chiralcel OD column (250 x 4.6 mm, 10 microm), hexane-ethanoldiethylamine-acetic acid (60 + 40 + 0.2 + 0.2, v/v/v/v) as the mobile phase, and a flow rate of 1.0 mL/min. MT isomers are separated by using a mobile phase with the same components in the following proportions (40 + 60 + 0.2 + 0.2, v/v/v/v) and a flow rate of 0.8 mL/min. Ultraviolet detection was at 276 nm for both analytes. The coefficients of variation (CVs) and average recoveries (ARs) for the R-enantiomers in samples A, B, C, D, and E were 1.15 and 101.06%, 0.74 and 99.25%, 1.05 and 102.57%, 0.84 and 101.57%, and 0.86 and 98.62%, respectively. The CVs and ARs for the S-enantiomers in samples A, B, C, D, and E were 1.33 and 98.87%, 0.99 and 100.76%, 1.17 and 101.69%, 1.26 and 100.39%, and 1.40 and 99.39%, respectively. The standard curves of R-AT, S-AT, R-MT, and S-MT showed good linearity over the concentration range studied with correlation coefficients of 0.9991, 0.998, 0.9988, and 0.999, respectively.

Photodegradation studies on Atenolol by liquid chromatography.

The photostability of the beta-blocker drug Atenolol was evaluated at pH 9, 7.4 and 4.0. The drug was exposed to UVA-UVB radiations and the photoproducts were detected by reversed phase LC methods. The photodegradation was found to increase with the pH value decreasing. The major photodegradation product at pH 7.4 was identified as 2-(4-hydroxyphenyl)acetamide. The LC method developed for routine analyses (column: C-18 Alltima; mobile phase: TEA acetate (pH 4; 0.01 M)-acetonitrile 96:4) was found to be suitable for the stability indicating determination of Atenolol in pharmaceutical dosage forms.

The Trial of Antihypertensive Interventions and Management (TAIM) Study. Final results with regard to blood pressure, cardiovascular risk, and quality of life.

The Trial of Antihypertensives Interventions and Management (TAIM) was a multicenter double-blind placebo-controlled clinical trial of drug and diet combinations for the treatment of mild hypertension among 878 participants, ages 21 to 65, 110% to 160% ideal weight, and with baseline diastolic blood pressure 90 to 100 mm Hg. The drugs used were placebo, chlorthalidone (25 mg/daily) or atenolol (50 mg/daily). The diets studied were usual, weight loss, sodium reduction/potassium increase. Trial end points were 6-month diastolic blood pressure change, cardiovascular risk change, and quality of life change. Either drug combined with weight loss produced the greatest blood pressure reduction of 15 mm Hg, compared to 8 mm Hg on placebo/usual diet. Adding sodium restriction to either drug did not enhance blood pressure lowering effect. Drugs outperformed diet in terms of antihypertensive effect. However, those on placebo and assigned to weight reduction who lost more than 4.5 kg and those on sodium restriction who reduced sodium to less than 70 mEq daily lowered blood pressure to a similar extent as those on either of the two drugs alone. Cardiovascular risk at 6 months relative to baseline ranged from 0.85 in weight loss/atenolol subgroup to 1.04 in the usual diet/chlorthalidone subgroup. Blacks were more responsive to chlorthalidone plus weight loss and whites to atenolol plus weight loss. Quality of life, as measured by scales of distress and well-being, was favorably affected by weight reduction. Although there were few side effects of the drugs and most patients improved on most parameters, sexual complaints were worsened among those on chlorthalidone and usual diet compared to placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Renin profile, race, and antihypertensive efficacy with atenolol and labetalol.

In this randomised double-blind parallel study, we compared the efficacy of labetalol and atenolol in a group of black (n = 33) and white (n = 34) hypertensives with uncomplicated essential hypertension after obtaining pretreatment renin profiles. After single-blind placebo (14-21 days), patients with standing diastolic BP between 105-119 mmHg were randomised to receive either labetalol (100-800 mg twice daily) or atenolol (50-100 mg once daily) to achieve a DBP less than 90 mmHg. Dosage titration occurred at weekly intervals for labetalol and biweekly for atenolol. The supine BP decrease with atenolol was -18/-14 vs. -6/-6 mmHg in whites vs. blacks respectively. With labetalol, it was -13/-12 in whites and -2/-7 mmHg in blacks. Standing BPs were: -19/-14 vs. -4/-5, whites vs. blacks with atenolol and -17/-17 vs. -19/-9 mmHg with labetalol. Neither labetalol nor atenolol was as effective in black compared with white hypertensives. The atenolol but not labetalol BP response was positively correlated with pretreatment renin values.