Simultaneous assay of sildenafil and desmethylsildenafil in neonatal plasma by ultra‐performance liquid chromatography–tandem mass spectrometry

Abstract

Sildenafil is used to treat pulmonary hypertension in neonatal and pediatric patients. Pharmacokinetic studies in these patients are complicated by the limited sample volume. We present the validation results of an assay method to quantitate sildenafil and desmethylsildenafil simultaneously in 50 microL of plasma. Deuterated sildenafil was used as an internal standard. After liquid-liquid extraction, analytes were separated on an ultra-performance liquid chromatography (UPLC)-column and quantified via tandem mass spectrometry. The calibration range was linear, with acceptable accuracy and a precision of <15% for both compounds. The lower limits of quantification were 1 ng/mL. Matrix effects were present, but inter-plasma batch variability was under 12%. The method was successfully applied to samples from a pharmacokinetic study into sildenafil pharmacokinetics in neonates, making maximum use of the limited number and amount of plasma samples available.

Development and validation of a gas chromatography‐mass spectrometric method for the determination of sildenafil and desmethyl‐sildenafil in whole blood

“…A few analytical methods have been published for the quantification of SDL alone [3,12,13] or with DSDL [1,[14][15][16] in human plasma [1,3,[12][13][14], blood [15] and urine [16]. Most of them are based on liquid chromatography and the only published GC/MS [16] is applied in urine samples, which are not suitable for therapeutic drug monitoring.…”

Dealing with matrix effect: should there be a cut‐off limit for signal ion suppression in quantitative assay validation?

“…In some situations, as in the example of sildenafil (Witjes et al, 2010), the amount of signal ion suppression may look alarming (i.e. >50%); however, it seems to have less of an impact on the performance of the assay.…”

“…In the example of sildenafil, the choice of deuterated internal standard (sildenafild 3 ) enabled a good assay performance in spite of a high signal ion suppression (Witjes et al, 2010). Norgestrel was selected as an internal standard for gestodene/ethinyl estradiol assay because of its structural resemblance to the analytes and structural properties that included ionization potential and comparable extraction recovery (Xiong et al, 2010).…”

Voltammetric Determination of Sildenafil Citrate and Furosemide at Composite Electrodes of Graphite-Paraffin for Use in Samples of Pharmaceutical and Toxicological Interests

“…Age no organismo como inibidor do simporte de Na + /K + /2Cl -, sua classificação como diurético de alça se deve por tal simporte ocorrer na alça do Henle (um segmento do néfron, sendo este último a principal unidade formadora de urina no rim). 21 Cerca de 65-70 % da furosemida são excretados integralmente pela urina. 23 A furosemida é indicada para o tratamento de edema pulmonar agudo, também é amplamente utilizado para tratamento de insuficiência cardíaca congestiva crônica e hipertensão arterial.…”