Method validation and determination of lisdexamfetamine and amphetamine in oral fluid, plasma and urine by LC–MS/MS

Abstract

Lisdexamfetamine (LDX) is a long-acting prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder and binge-eating disorder symptoms. In vivo hydrolysis of LDX amide bond releases the therapeutically active d-amphetamine (d-AMPH). Since toxicological tests in biological samples can detect AMPH from the use of some legal medications, efficient methods are needed in order to correctly interpret the results. The aim of this study was to develop and validate an LC-MS/MS method for the simultaneous quantification of LDX and its main biotransformation product AMPH in human oral fluid, plasma and urine. Calibration curve range for both analytes was 1-128 ng/mL in oral fluid and plasma and 4-256 ng/mL in urine, being the lowest concentration the limit of quantification. Accuracy of the determined values of the target analytes for the five control levels ranged from 94.8 to 111.7% for oral fluid, from 91.3 to 100.2% for plasma and from 94.8 to 109.8% for urine. Imprecision for the five control levels did not exceeded 12.8% for oral fluid, 16.2% for plasma and 17.1% for urine. The method developed for the three matrices was validated and was also successfully applied to assess real samples, showing for the first time the detection of LDX in oral fluid.

Lisdexamfetamine and amphetamine pharmacokinetics in oral fluid, plasma, and urine after controlled oral administration of lisdexamfetamine

“…Samples of oral fluid, plasma and urine were analyzed for LDX and AMPH using the liquid chromatography‐mass spectrometry (LC‐MS/MS) method previously validated by our research group (Comiran et al, 2017). Method lower limit of detection was the same for both analytes, 1 ng/ml in oral fluid and plasma and 4 ng/ml in urine.…”

“…The simple detection and quantification of LDX and AMPH in biological fluids such as blood, urine and, more recently, oral fluid (Comiran et al, 2017) has already been reported, and the pharmacokinetics of these analytes has been extensively described just for plasma (Adler, Alperin, Leon, & Faraone, 2017; Biederman et al, 2007; Boellner, Stark, Krishnan, & Zhang, 2010; Comiran, Kessler, Fröehlich, & Limberger, 2017; Ermer et al, 2012, 2011; Ermer, Corcoran, & Martin, 2015; Ermer et al, 2013a; Ermer et al, 2013b; Jasinski & Krishnan, 2009a, 2009b; Krishnan, Pennick, & Stark, 2008; Krishnan & Stark, 2008; Krishnan & Zhang, 2008; Pennick, 2010, 2013; Roesch et al, 2013; Rowley et al, 2012). To the best of the authors' knowledge, the pharmacokinetic profile of LDX and its main metabolite, d ‐AMPH, in oral fluid and urine has not been described so far.…”

Enantiomeric separation and quantification of R/S‐amphetamine in serum using semi‐automated liquid‐liquid extraction and ultra‐high performance supercritical fluid chromatography‐tandem mass spectrometry

“…20 As this additive caused extensive ion suppression in the electrospray ionization (ESI) source, a solid phase extraction method was required to obtain satisfactory signal of the lowest calibration level in urine. In serum the concentrations are considerably lower than in urine 21,22 and even with sample extraction the analytical signal for the lowest standard was not sufficient using this UPC 2 method. 19 In 2019, Segawa et al 23 published a method for chiral analysis of impurities of methamphetamine such as R/S-amphetamine.…”

Development and Validation for Estimation of Related Substances of Lisdexamphetamine Dimesylate by Rp-HPLC

“…Lisdexamphetamine dimesylate (LIS) is a drug of choice for ADHD (Attention Deficit Hyperactivity Disorder) 1 and binge eating disorder. 2 It is inactive in nature because it is a prodrug which shows therapeutic effect after metabolism.…”

“…Pure drug is hydrophilic in nature so it is freely soluble in water. 1 Enzyme hydrolysis takes place after oral administration. Lisdexamphetamine breaks into L-lysine, a naturally occurring essential amino acid and active d-amphetamine which is the component responsible for the drug's activity.…”