Carbamazepine is an early anticonvulsant still used today in the treatment of several forms of epilepsy. An active metabolite in the human body contributes to its pharmacological effect. Carbamazepine metabolism has high inter-individual variability, such that it is relatively difficult to establish a direct link between dose and concentration, or between concentration and pharmacological effect.Carbamazepine is thus a good candidate for therapeutic drug monitoring (TDM). Good UV specific absorbance and high plasmatic concentrations allow for the use of UV detection, which is often more accessible than other methods of detection.This paper presents several methods used for the detection of carbamazepine in plasma, methods that are capable of detecting drug and metabolites at adequate levels/ acceptance criteria. These methods have possible application not only in pharmacokinetic, bioequivalence, and permeability studies, but also in the therapeutic drug monitoring of carbamazepine.Acne conglobata is a rare, severe form of acne vulgaris characterized by the presence of comedones, papules, pustules, nodules and sometimes hematic or meliceric crusts, located on the face, trunk, neck, arms and buttocks.
An isocratic simple and rapid HPLC-UV method has been developed and validated for the determination of carbamazepine (CBZ) in human plasma, using nitrazepam (NTZ) as internal standard. Separation was carried out on a C18 column with a mobile phase composed of water:acetonitrile (55:45 v/v), delivered at a flow rate of 1 mL/min. Liquid-liquid extraction with ethyl acetate was used for the isolation of the analytes from plasma. Development of the method was based on a design of experiments (DOE) approach. A 2 3 full factorial design with central points was used in order to select the experimental parameters, while considering peak asymmetry, resolution between CBZ and the internal standard and retention time as responses. Overall, optimization of the analysis parameters was performed using Derringer's desirability function and overlay contour plots. The method was fully validated in the concentration range of 0.1 -20 µg/mL, which included the entire therapeutic range of CBZ (4 -12 µg/mL). The method is simple, rapid (with a total analysis time of 5 minutes) and can be applied in routine clinical investigations.
RezumatA fost dezvoltată și validată o nouă metodă lichid cromatografică pentru determinarea cantitativă a carbamazepinei (CBZ) din plasma umană, utilizând nitrazepamul ca standard intern. Separarea a fost realizată pe o coloană de tip C18, utilizând o fază mobilă conținând un amestec de apă și acetonitril, în raport volumic 55:45. Debitul fazei mobile a fost de 1 mL/min. Izolarea analiților din probele de plasmă s-a realizat prin extracție lichid-lichid, folosind acetatul de etil drept solvent de extracție. Dezvoltarea metodei a fost realizată utilizând tehnici de design experimental. A fost utilizat un design de tip factorial, cu trei factori la 2 nivele (2 3 ), considerându-se ca și răspunsuri asimetria picurilor, rezoluția între CBZ și standardul intern, precum și timpul de retenție al analiților. Pentru optimizarea parametrilor, s-au utilizat gradul de dezirabilitate și graficele de contur suprapuse. Metoda a fost validată pe un interval de concentrații între 0,1 și 20 µg/mL, care include zona terapeutică a CBZ (4 -12 µg/mL). Metoda este simplă, rapidă (cu un timp total de analiză de 5 min) și poate fi aplicată în monitorizarea terapeutică a CBZ.
Carbamazepine is an early anticonvulsant still used today in the treatment of several forms of epilepsy. An active metabolite in the human body contributes to its pharmacological effect. Carbamazepine metabolism has high inter-individual variability, such that it is relatively difficult to establish a direct link between dose and concentration, or between concentration and pharmacological effect.Carbamazepine is thus a good candidate for therapeutic drug monitoring (TDM). Good UV specific absorbance and high plasmatic concentrations allow for the use of UV detection, which is often more accessible than other methods of detection.This paper presents several methods used for the detection of carbamazepine in plasma, methods that are capable of detecting drug and metabolites at adequate levels/ acceptance criteria. These methods have possible application not only in pharmacokinetic, bioequivalence, and permeability studies, but also in the therapeutic drug monitoring of carbamazepine.Acne conglobata is a rare, severe form of acne vulgaris characterized by the presence of comedones, papules, pustules, nodules and sometimes hematic or meliceric crusts, located on the face, trunk, neck, arms and buttocks.
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