Simultaneous quantification of buprenorphine, norbuprenorphine, buprenorphine-glucuronide and norbuprenorphine-glucuronide in human umbilical cord by liquid chromatography tandem mass spectrometry

Abstract

A LCMS method was developed and validated for the simultaneous determination of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc) and norbuprenorphine glucuronide (NBUP-Gluc) in human umbilical cord. Quantification was achieved by selected ion monitoring of precursor ions m/z 468.4 for BUP; 414.3 for NBUP; 644.4 for BUP-Gluc and 590 for NBUP-Gluc. BUP and NBUP were identified by MS 2 , with m/z 396, 414 and 426 for BUP, and m/ z 340, 364 and 382 for NBUP. Glucuronide conjugates were identified by MS 3 with m/z 396 and 414 for BUP-Gluc and m/z 340 and 382 for NBUP-Gluc. The assay was linear 1-50 ng/g. Intra, interday and total assay imprecision (%RSD) were <14.5%, and analytical recovery ranged from 94.1% to 112.3% for all analytes. Extraction efficiencies were >66.3%, and process efficiency >73.4%. Matrix effect ranged, in absolute value, from 3.7% to 27.4% (CV<21.8%, n=8). The method was selective with no endogenous or exogenous interferences from 41 compounds evaluated. Sensitivity was high with limits of detection of 0.8 ng/g. In order to prove method applicability, an authentic umbilical cord obtained from an opioid-dependent pregnant woman receiving BUP pharmacotherapy was analyzed. Interestingly, BUP was not detected but concentrations of the other metabolites were NBUP-Gluc 13.4 ng/g, BUP-Gluc 3.5 ng/g and NBUP 1.2 ng/g.

Confirmatory analysis of buprenorphine, norbuprenorphine, and glucuronide metabolites in plasma by LCMSMS. Application to umbilical cord plasma from buprenorphine-maintained pregnant women

“…No derivatization is required and glucuronide metabolites can be quantified without the need for costly and time-consuming hydrolysis. LCMS and LCMSMS have been applied for BUP and metabolites’ analysis in a wide variety of matrices including, urine [1,19–28], hair [21,23,25,29–32], sweat [33], meconium [34], breast milk [35], placenta [36], and umbilical cord [37]. In plasma, several methods were published for BUP alone [18,38], BUP and NBUP [23,39–41]; BUP, NBUP, and glucuronides after hydrolysis [25,42]; BUP, NBUP and BUPG [43]; and all four analytes [1,15,44].…”

High-sensitivity analysis of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in plasma and urine by liquid chromatography–mass spectrometry

“…Methods for quantification of buprenorphine and one or more major metabolites in plasma and/or urine include immunoassay [22,23], gas chromatography with various detectors [24–28], HPLC with single quadrupole or tandem quadrupole mass spectrometry [13,29–35], and most recently UPLC methods with mass spectrometry [36–40]. Various methods of sample preparation have also been described, including protein precipitation [40], liquid/liquid extraction [39], and solid-phase extraction [37,41,42].…”

The Detection of 1-Palmitoyl-2-oleoyl-&lt;i&gt;sn&lt;/i&gt;-glycero-3-phosphoethanol and Ethyl Glucuronide in Human Umbilical Cord

“…The detection of benzoylecgonine in UC tissue has been used as forensic evidence of maternal drug use [26] and that interpretation was upheld on appeal to the South Carolina Supreme Court in 2008 [27]. Reports of UC for the detection of amphetamines [28], opiates [29][30][31], caffeine [32] and tobacco metabolites [33,34] have been published in recent years.…”