Open Access
Subscription Access
Open Access
Subscription Access
Validated HPLC Method for the Analysis of Clozapine in Rat Plasma and its Application to Pharmacokinetics
Subscribe/Renew Journal
As a prerequisite to the determination of pharmacokinetic parameters of clozapine in rats, an HPLC method using UV detection was developed and validated. Clozapine and the internal standard, ambroxol were extracted from plasma samples using hexane and isoamyl alcohol (98.5:1.5 v/v) solutions. Chromatographic separation was achieved on a phenomenex C18 column (5 µ; 25 cm x 4.6 mm id) using a mobile phase of ACN/0.5% triethylamine solution in Ammonium acetate buffer of pH 5 in the ratio of 40:60 at a flow rate of 1.5 ml/min. Detection was at 263 nm. The calibration curve was linear from 50-500 ng/ml. The Intra-day accuracy ranged between 99.99% and 100.05% with precision of 0.006% and 0.03%. The Inter-day accuracy ranged between 99.98% and 100.01% with precision of 0.010% and 0.058%. The main pharmacokinetic parameters for rats were determined after a single intravenous administration of 100 mg/kg clozapine are t1/2, 0.0614 h; AUC0-, 83.368 ng.hr/ml; Cmax, 36.16 ng/ml; Tmax, 0.5 hrs; Keli, 11.2847 hrs-1.
Keywords
Clozapine, Plasma, Bioavailability, HPLC
Subscription
Login to verify subscription
User
Font Size
Information
- Daniel DG and Whitcomb, S.R. Treatment of the refractory schizophrenic patient. Journal of Clinical Psychiatry. 59: 1998: 38-48.
- Brambilla P, Barale F and Caverzasi E. Clozapine-treated subjects with treatment-resistant schizophrenia: a systematic review of experimental and observational studies. International Journal of Clinical Psychopharmacology. 17: 2002: 189–195.
- Meltzer HY. Treatment-resistant schizophrenia--the role of clozapine. Current Medical Research and Opinion. 14: 1997: 1-20.
- Kerwin RW and Anusha B. Management of clozapine-resistant schizophrenia Anusha Bolonna. Advances in psychiatric treatment. 11: 2005: 101.
- Fitton A and Heel RC. Clozapine: a review of pharmacological properties and therapeutic use in schizophrenia. Drugs. 5: 1990: 722-725.
- Lieberman JA. Atypical antipsychotic drugs as a first-line treatment of schizophrenia: a rationale and hypothesis. Journal of Clinical Psychiatry. 57(11): 1996: 68-71.
- Richelson E. Receptor pharmacology of neuroleptics: Relation to clinical effects. Journal of Clinical Psychiatry. 60: 1999: 5-14.
- Jann MW and Grimsley SR. Pharmacokinetics and pharmacodynamics of clozapine Clinical Pharmacokinetics. 24: 1993: 161-176.
- Patricia Z, Yuval M, Abraham W and Avi B. Clozapine- InducedEosinophilia andSwitch toQuetiapine ina Patient with Chronic Schizophrenia with Suicidal Tendencies. Isralian Journal of Psychiatry Related Sciences. 44(1): 2007: 54–56
- Ackenheil M. Clozapine–pharmacokinetic investigations and biochemical effects in man. Psychopharmacology. 99: 1989: S32-37.
- Wongwiwat T, Khanogwan K, Suda V, Jureeporn K, Arporn T, Prapawadee P, Siriporn T, Srisaard J, Veerapol K and Wichittra T. STEADY STATE BIOEQUIVALENCE STUDY OF CLOZAPINE TABLET IN SCHIZOPHRENIC PATIENTS. Journal of pharmacy and pharmaceutical sciences. 8(1): 2005: 47-53.
- Schaber G, Stevens I, Gaener HJ. Dietz K and Breyer-Pfaff U. Pharmacokinetics of clozapine and its metabolites in psychiatric patients: plasma protein binding and renal clearance.British Journal of Clinical Pharmacology. 46(5): 1998: 453–459.
- Moiser KE, Song J, McKay G, Hubbard JW and Fang J. Determination of clozapine N-Oxide in dog plasma using hig performance liquid chromatography. Journal of Chromatography B. 783(2): 2003: 377-382.
- Manjunath K and Venkateswaralu V. Validated HPLC method for the determination of clozapine in rat serum and its application to pharmacokinetics. Indian Journal of Pharmaceutical Sciences. 67(4): 2005. 448-452. Ma F, Lau CE. Determination of clozapine and its metabolite, N-desmethylclozapine in serum microsamples by high performance liquid chromatography and its application to pharmacokinetics in rats. Journal of Chromatography B. 712 (1): 2003:193-198
Abstract Views: 370
PDF Views: 3