A dried urine spot test to simultaneously monitor Mo and Ti levels using solid sampling high-resolution continuum source graphite furnace atomic absorption spectrometry
Highlights
► Deposition of urine on clinical filters facilitates home-based collection schemes. ►SS HR CS GFAAS enables direct determination of Mo and Ti in urine dried spots. ► These elements may be used as biomarkers to detect prosthesis malfunctioning. ► The way in which the sample is deposited in the filter is a key to proper quantitation. ► The use of matrix-matched urine standards for calibration is recommended.
Introduction
Ti has no known biological role in humans and it has long been considered as biologically inert and, therefore, it seems ideal for metallic implants, such as dental and orthopedic replacements (joint, hip or spinal implants, to name a few) [1]. Ti quantification in biological fluids could have been considered as anecdotic until a few years ago, as its measurement did not have any clear clinical interest.
On the other hand, Mo is an essential trace element for plants, animals and microorganisms. Up to date, Mo is considered as practically non-toxic to humans, albeit patients with acute Mo poisoning exhibit symptoms similar to those of Cu deficiency or abnormal sulfur metabolism. Therefore, as discussed before for Ti, Mo has not been normally monitored in clinical samples. Furthermore, these elements, and in particular Ti, are not easy to quantify at basal levels by graphite furnace atomic absorption spectrometry (GFAAS) and or by quadrupole-based inductively coupled plasma-mass spectrometry (Q-ICP-MS) [1].
However, the situation has changed as a consequence of the use of metallic implants in joint-replacement surgery, since the concentration of some metals in blood and/or urine has been considered as potential indicator of implant performance. These implants are made with alloys typically containing Cr, Co, Mo and/or Ti. Thus, the monitoring of these analytes in a variety of clinical specimens, such as serum, urine, whole blood, erythrocytes and joint fluid, has become of great interest [2].
A number of investigations have shown that these elements modestly raise its concentration in these matrices after the implant, but then they reach a plateau when the prosthesis is well functioning [3], [4], [5], [6]. Most importantly, it has been demonstrated that a notable increase in the concentration of these metals may occur in mal-functioning prostheses, including examples where it was not possible to visualize this fail (abnormal wear, corrosion or displacement of the implant) by diagnostic imaging techniques, in spite of the pain referred by the patient. These abnormal metal concentrations proved to be evidence of several kinds of unstable prostheses, which had to be replaced surgically [6], [7], [8], [9]. As a consequence of these cases, increasing attention is paid to the monitoring of these metallic elements in clinical samples [10].
On the other hand, there is a growing interest in the deposition of biological fluids, such as blood [11] or urine [12], on filter papers (FP), giving rise to what is generically called dried matrix spots (DMS). This sampling methodology offers significant advantages in terms of logistics for clinical analysis. In the case of urine, this is certainly not a particularly difficult fluid to collect. However, many urinary metabolites have a poor stability, thus requiring restrictive precautions, especially for sample transport and storage. Therefore, the deposition of urine on clinical filter paper (giving rise to dried urine spots, DUS) becomes an attractive alternative due to the ease of preservation [13]. Furthermore, DUS samples can be easily mailed over distances, even overseas, for analysis at referral centers. This aspect is very interesting in various clinical contexts, such as carrying out large-population based studies [14], or monitoring of chronic patients or patients that have undergone a certain type of surgery (e.g., patients with implants). DUS specimens should be easily prepared at home by the own patients, helping to reduce their number of visits to the clinic, and improving their life quality. As a result, any efforts to develop analytical methods based on DUS samples for as many analytes as possible are regarded with interest in the clinical field.
There are several examples in the literature dealing with the analysis of dried urine on clinical filter paper, but the majority are focused on detection of metabolites and drugs [15]. Very little work has been carried out aiming at elemental monitoring, on DUS [16], [17] (using laser ablation–inductively coupled plasma–mass spectrometry, LA–ICP–MS), or in general on DMS [18], [19]. One of the reasons for this limited work may be that, even though the use of this technique looks very appealing for implementing home-based collection methods [20], it presents a further problem for analysis: the transformation of a relatively simple liquid sample (urine) into a solid one (DUS), which typically requires additional work (e.g., digestion or extraction of the analytes of interest from the filter paper prior to analysis [21]). Instead, the use of solid sampling techniques allowing for the direct analysis of DMS represents an attractive alternative, increasing sample throughput and minimizing risks of losses/contamination, although quantification is not always simple owing to matrix-effects [16], [19], [22], [23].
The purpose of this work is to develop a fast method for the direct and simultaneous determination of Mo and Ti in DUS samples prepared with standardized clinical filter paper. As discussed before, such method could be useful for monitoring the evolution of patients with prostheses. For this purpose, we are exploring the use of solid sampling high-resolution continuum source graphite furnace atomic absorption spectrometry (SS HR CS GFAAS). To the best of the author's knowledge, the use of GFAAS has not been evaluated yet for direct analysis of DUS. However, the potential of “classic” line source GFAAS for direct analysis of solid samples [24], [25], including determination of Pb in blood deposited in FP [18], is well-established. Moreover, this potential has been significantly enhanced with the arrival of HR CS GFAAS [26], [27], [28], which offers improved capabilities for the detection and correction of spectral interferences, as well as for the simultaneous monitoring of several elements under certain conditions [29], [30], [31], although developing simultaneous methods, as will be required in this work, is not always straightforward [29]. This aspect, together with the investigation of the distribution of the target elements on the DUS and the development of a suitable calibration approach, will be the main topics investigated in the current work.
Section snippets
Instrumentation
The measurements of Mo and Ti in dried urine spots were carried out using a high-resolution continuum source atomic absorption spectrometer, ContrAA 700, commercially available from Analytik Jena AG (Jena, Germany) and equipped with both graphite furnace and flame atomizers. The optical system comprises a xenon short-arc lamp (GLE, Berlin, Germany) operating in “hot-spot” mode as the radiation source, a high-resolution double echelle monochromator (DEMON) and a linear CCD array detector with 588
Initial experiments with liquid samples
As discussed in the introduction, there is now supported evidence that the performance of metallic prosthesis in implanted patients could be assessed by the monitoring of elements commonly used in metallic alloys in blood and/or urine, insomuch that a significant increase in their levels would reflect its release from the implant and, therefore, that the prosthesis is mal-functioning [6]. In this regard, Mo and/or Ti are present in practically all types of metallic implants, so these appear as
Conclusions
This work reports a general methodology for the direct determination of trace elements at the μg L− 1 level in urine samples deposited on clinical filter papers by means of solid-sampling HR CS GFAAS. The method proposed permits the simultaneous determination of Mo and Ti, which could be relevant in the context of monitoring the functioning of metallic implants in humans.
The method obviously benefits from the performance of HR CS GFAAS instrumentation, which permits the simultaneous measurement
Acknowledgments
This work has been funded by the Spanish Ministry of Economy and Competitiveness (project CTQ2012-33494) and the Aragón Government (Fondo Social Europeo).
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