A quantitative LC–MS/MS method for simultaneous determination of cocaine and its metabolites in whole blood

Abstract

As new metabolic pathways of cocaine were recently identified, a high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine cocaine and nine cocaine-related metabolites in whole blood samples. One-step solid phase extraction was used to extract all of the ten compounds and corresponding internal standards from blood samples. All compounds and internal standards extracted were separated on an Atlantis T3 (100Å, 3 µm, 2.1 mm × 150 mm I.D) column and detected in positive ion and high sensitivity mode with multiple reaction monitoring. This method was validated for its sensitivity, linearity, specificity, accuracy, precision, recovery, and stability. All of the ten compounds were quantifiable ranging from the lower limit of quantification (LLOQs) of ~10 nM (1.9–3.2 ng/ml) to ~1000 nM (190–320 ng/ml) without any interfering substance. Accuracy and precision were determined, and both of them were within the acceptance criteria of the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. The recovery was above 66.7% for all compounds. Stability tests demonstrated the stability of compounds under different storage conditions in whole blood samples. The method was successfully applied to a pharmacokinetic study with co-administration of cocaine and alcohol in rats.

A fast and simple approach for the quantification of 40 illicit drugs, medicines, and pesticides in blood and urine samples by UHPLC‐MS/MS

“…For the interday accuracy, the values found were within the range of 1.9% (high MDMA control) to 18.6% (low aldicarb control). Chen et al reported similar accuracy values. Arora et al found values between 0.1% and 19% in the precision assay and 82.1% to 119% in the accuracy of the LC‐MS method.…”

“…A significant matrix effect of blood was observed for some substances (aldicarb and bromazepam [increase of signal] and phenytoin and valproic acid [suppression]). However, they are not considered as discrepant compared with those published in the literature with similar methodologies . In addition, since the sensitivity of the method was considered satisfactory, the matrix effect did not negatively influence the application of the method.…”

“…The with the values found in similar studies. 25,26 37,40 In addition, since the sensitivity of the method was considered satisfactory, the matrix effect did not negatively influence the application of the method. The matrix effect results for analytes were described in Table 3.…”

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“…Its TDM is necessary; it is fulfilled through the measurement of trough plasmatic concentrations14 . HPLC-UV is an accurate method but needs an extended step of extraction followed by the injection in the HPLC-UV system15 .…”

Aplicação da análise multivariada para o mapeamento dos casos de intoxicações agudas atendidos no Centro de Controle de Intoxicações da cidade de São Paulo

“…As precisões intra e inter-dia foram consideradas aceitáveis Um efeito matriz relevante foi observado para algumas substâncias (aldicarbe, e bromazepam (aumento de sinal) e fenitoína (supressão). No entanto, não são considerados discrepantes comparados aos publicados na literatura com metodologias similares (CHEN et al, 2016;SEMPIO et al, 2014). Além disso, como a sensibilidade do método foi considerada satisfatória, o efeito matriz não influenciou negativamente na aplicação do método.…”