ABSTRACT
Naratriptan Hydrochloride is a triptan drug used for the treatment of migraine headaches and is a selective 5-hydroxytryptamine 1 receptor subtype agonist. Two simple, precise and economical UV-Spectrophotometric methods have been developed for the determination of Naratriptan Hydrochloride in pharmaceutical dosage form. In Method I, zero order spectrum of Naratriptan Hydrochloride was derivatized into first order (Δ λ = 2, scaling factor = 9) using UV-probe software and the amplitude of the trough was recorded at 232.2 nm. While in ‘Method II’, area under curve (AUC) of the first order derivative spectrum was selected between 294.20 – 299.00 nm. In Method I and II, Naratriptan Hydrochloride obeyed linearity in the concentration range of 10 - 60 μg/ml. The coefficient correlation (r2) in Method I and II were found to be r2 = 0.999 and r2= 0.998, respectively. The % amounts of Naratriptan Hydrochloride quantified by Method I and Method II was found to be 98.79 % and 99.43%. The developed methods were validated statistically and by recovery studies.
ABSTRACT
The authors developed a simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of naratriptan (NP) in human plasma using naratriptan-d3 (NPD3) as an internal standard (IS). Chromatographic separation was performed on a Zorbax SB-C18, 75 x 4.6 mm, 3.5 µm column with an isocratic mobile phase composed of 0.1 percent formic acid : acetonitrile (50:50 v/v), at a flow-rate of 0.6 mL/min. NP and NPD3 were detected with proton adducts at m/z 336.5→98.0 and 339.4→101.0 in selected reaction monitoring (SRM) positive mode, respectively. The liquid-liquid extraction method was used to extract the NP and NPD3. This method was validated over a linear concentration range of 0.1-25.0 ng/mL with a correlation coefficient of (r2) > 0.9998. The Intra-day and Interday precision was found to be 1.8 to 3.6 percent, and 2.3 to 2.6 percent, and accuracy to be 101.7- 104.2 percent and 101.8 to 102.9 percent, respectively. NP was found to be stable throughout freeze-thaw (three cycles), bench top and auto sampler stability studies. This method was successfully applied for the analysis of plasma samples following oral administration of NP (2.5 mg) in 31 healthy Indian male human volunteers under fasting conditions.
Os autores desenvolveram um método simples, sensível e específico de cromatografia líquida-espectrometria de massa-tandem (LC-MS/MS) para a quantificação de naratriptan (NP) em plasma humano empregando naratriptan-d3 (NPD3) como padrão interno de referência (IS). A separação cromatográfica foi realizada em coluna Zorbax SB-C18, 75 x 4,6 mm, 3,5 μm com fase móvel isocrática composta por 0,1 por cento ácido fórmico : acetronitrila (50:50 v/v) e taxa de fluxo de 0,6 mL/min. NP e NPD3 foram detectados com adutos de prótons a m/z 336.5→98.0 e 339.4→101.0 in em modo positivo do tipo monitoramento de reação selecionada (SRM), respectivamente. Extração líquido-líquido foi empregada para extrair NP e NPD3, sendo o método validado para uma faixa linear de concentração de 0,1-25,0 ng/mL resultando em coeficiente de correlação (r2) > 0,9998. A variação intra e interdia observada para precisão foi de 1,8 a 3,6 por cento e 2,3 a 2,6 por cento, respectivamente; para exatidão a variação foi de 101,7 a 104,2 por cento e 101,8 a 102,9 por cento, respectivamente. O NP se mostrou estável frente a processos de congelamento-descongelamento (3 ciclos), e estudos de estabilidade de bancada e amostragem automática. O método desenvolvido foi aplicado com sucesso para a análise de amostras de plasma após a administração oral de 2,5 mg de NP em 31 voluntários humanos, de nacionalidade indiana, sexo masculino, sob condições aceleradas.