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Arzneimittelforschung 2008; 58(11): 551-556
DOI: 10.1055/s-0031-1296556
CNS-active Drugs · Hypnotics · Psychotropics · Sedatives
Editio Cantor Verlag Aulendorf (Germany)

Bioequivalence of Two Commercial Preparations of Escitalopram Oxalate/Clonazepam Using a Liquid Chromatography-Electrospray Mass Spectrometry Method

Sangita Agarwal
1   Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
,
Kadajji Veeran Gowda
1   Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
,
Perumal Senthamil Selvan
1   Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
,
Tapas Kumar Chattaraj
2   Nil Ratan Sircar Medical College and Hospital, Kolkata, India
,
Tapan Kumar Pal
1   Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
› Author Affiliations
Further Information

Publication History

Publication Date:
19 December 2011 (online)

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Abstract

Objective:

A randomized, two-way crossover study was conducted in 24 fasting healthy male volunteers of Indian origin to compare the bioavailability of two brands of a fixed dose combination of escitalopram oxalate (CAS 219861-08-2) 10 mg and clonazepam (CAS 1622-61-3) 0.5 mg tablets, using Estomine-zee® as test and a commercially available formulation as the reference product. The pharmacokinetics of escitalopram oxalate and clonazepam individually after oral administration of tablet formulation has been extensively evaluated in adult volunteers. However, no published data are available regarding the pharmacokinetics and bioavailability of this particular fixed dose combination.

Method:

The trial was designed as a randomized, balanced, open-label, 2-period cross-over study. The drug was administered with 240 ml of water after a 10-h overnight fasting on two treatment days separated by a 21-day washout period. After dosing, serial blood samples were collected for a period of 96 h. Plasma harvested from blood was analyzed by simple rapid, selective and validated liquid chromatography-electrospray mass spectrometry (LC-ESI-MS/MS) using diazepam (CAS 439-14-5) as an internal standard.

Results:

The calibration curves were found to be linear in the range of 1–25 ng/ml and 1–10 ng/ml for escitalopram oxalate and clonazepam, respectively, with a mean correlation coefficient of more than 0.99. No statistically significant differences were obtained between the two products with respect to the mean concentration-time profiles or in the pharmacokinetic parameters, including the area under the serum concentration-time curve from the present study.

Conclusion:

Based on the statistical inferences, it was concluded that the test product is bioequivalent to the reference product. Both preparations were well tolerated with no adverse reactions throughout the study.

Key words

Antidepressants - Anxiolytics - CAS 1622-61-3 - CAS 219861-08-2 - Clonazepam, bioequivalence, combination with escitalopram oxalate, LC-ESI-MS/MS - Escitalopram oxalate, bioequivalence, combination with clonazepam, LC-ESI-MS/MS
 

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