Pipette tip-electrospray mass spectrometry for determining opioids in urine, from on-site micro-handling to high-throughput centrifugal microextraction

Pipette tip-electrospray is a useful technique that synergically combines sample preparation and ambient ionization mass spectrometry for the rapid analysis of samples. In this work, the development of pipette tip extraction (PTE) is evaluated under two workflows that can be adapted to different analytical scenarios. Micro-handling PTE (MH-PTE) is an inherently portable technique that can be on-site applied. Centrifugal PTE (C-PTE), firstly presented here, allows a high sample throughput just requiring a benchtop centrifuge. The combination of both MH-PTE and C-PTE with pipette tip-electrospray is evaluated in this work for determining codeine and morphine, two metabolically related drugs, in urine and applied to the analysis of real samples. In the case of MH-PTE, intended to be on-site applied, the chemical stability of the analytes once extracted in the tips plays a crucial role. This stability has been studied in detail, simulating several transport/storage conditions compatible with regular postal services. The analytical features of both combinations are similar, although C-PTE provides a better sensitivity in terms of limit of detection (0.3 µg L⁻¹ for codeine and 0.6 µg L⁻¹ for morphine) compared to MH-PTE (0.6 µg L⁻¹ for codeine and 1.5 µg L⁻¹ for morphine). Moreover, the sample throughput provided by C-PTE is higher (up to 72 samples h⁻¹) than that provided by MH-PTE (up to 12 samples h⁻¹).