Modification of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method targeting lysergic acid diethylamide (LSD) and its primary metabolite (OH-LSD) to include nine LSD analogs.

A validated LC-MS/MS method can detect LSD, its primary metabolite OH-LSD, and nine LSD analogs in urine with a limit of detection of 0.1 ng/mL. The method uses automated sample preparation and a modified analytical column and gradient. Analysis of 325 urine specimens found no LSD analogs, but the procedure is suitable for laboratories expanding their testing scope. Automated preparation reduces manual handling without increasing analytical time. Detection may improve as reference standards for metabolic products become available. The validated procedure supports routine analysis and surveillance of these emerging substances.

Study at a glance

Abstract

A variety of LSD analogs have emerged in recent years with dual purposes of avoiding prosecution from possession while providing new options for those willing to experiment with hallucinogenic drugs. In this study, a previously published automated sample preparation method for LSD and its primary metabolite (OH-LSD) was utilized to extract LSD, OH-LSD, and nine LSD analogs from urine. The liquid chromatography tandem mass spectrometry (LC-MS/MS) method was modified from the previously published LC conditions to utilize a different analytical column and gradient elution program. Mobile phases of 10 mM ammonium formate with 0.1% formic acid in deionized water (mobile phase A) and 0.1% formic acid in methanol (mobile phase B) were employed. The method was validated to ANSI/ASB Standard 036 with a 0.1 ng/mL limit of detection for all analytes and was utilized for the analysis of 325 urine specimens. Although no LSD analogs were observed in the samples analyzed, this validated method was demonstrated to be suitable for the analysis of these compounds in laboratories seeking to expand their testing scope. Automated sample preparation allows for the efficient analysis of these analytically challenging compounds with minimal manual handling. Additionally, there was no increased analytical time burden when the LC column and gradient were modified to target nine additional analytes. Detection may improve as new reference standards are developed to allow laboratories to focus on the metabolic products of these analogs. For now, this validated procedure can assist with the routine analysis and surveillance of these emerging substances.