Bioequivalence of two commercial preparations of escitalopram oxalate/clonazepam using a liquid chromatography-electrospray mass spectrometry method.
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.


METHODS
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.


CONCLUSIONS
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.
Agarwal
Sangita
S
Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Gowda
Kadajji Veeran
KV
Selvan
Perumal Senthamil
PS
Chattaraj
Tapas Kumar
TK
Pal
Tapan Kumar
TK
D000328:Adult; D019540:Area Under Curve; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000493:pharmacokinetics*; D002998:Clonazepam / Q000493:pharmacokinetics*; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D018757:GABA Modulators / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics*; D021241:Spectrometry, Mass, Electrospray Ionization; D013810:Therapeutic Equivalency; D055815:Young Adult
D015283:Citalopram; D002998:Clonazepam; D004338:Drug Combinations; D018757:GABA Modulators; D017367:Selective Serotonin Reuptake Inhibitors